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TRANSCRIPT
CDCIDSA COVID-19 Clinician CallJune 26 2021
bull 69th in a series of weekly calls initiated by CDC as a forum for information sharing among frontline clinicians caring for patients with COVID-19
bull The views and opinions expressed here are those of the presenters and do not necessarily reflect the official policy or position of the CDC or IDSA Involvement of CDC and IDSA should not be viewed as endorsement of any entity or individual involved
bull This webinar is being recorded and can be found online at wwwidsocietyorgcliniciancalls
Welcome amp IntroductionDana Wollins DrPH MGCVice President Clinical Affairs amp Guidelines IDSA
1
TODAYrsquoS CALL
Myocarditis after COVID-19 mRNA Vaccine
Plus Vaccine QampA
Overview of Myocarditis and Pericarditis Matt Oster MD MPHDirector Childrenrsquos Cardiac Outcomes Research ProgramSibley Heart Center Cardiology Childrenrsquos Healthcare of AtlantaMedical Officer CDC Center on Birth Defects amp Developmental Disabilities Centers for Disease Control and Prevention COVID-19 Response
2
COVID-19 Vaccine Safety Updates Tom Shimabukuro MD MPH MBACaptain US Public Health ServiceDeputy Director Immunization Safety OfficeCenters for Disease Control and Prevention
Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesJudith A Guzman-Cottrill DOProfessor of Pediatrics Division of Infectious DiseasesOregon Health amp Science University School of Medicine
COVID-19 mRNA Vaccines in Adolescents and Young Adults Benefit-Risk DiscussionAmanda Cohn MDChief Medical Officer COVID-19 Task ForceChief Medical Officer National Center for Immunization amp Respiratory DiseasesCaptain US Public Health ServiceCenters for Disease Control and Prevention
Question Use the ldquoQampArdquo Button
Comment Use the ldquoChatrdquo Button
3
Myocarditis and Myopericarditis after COVID-19 Vaccination
A Case SeriesCDCIDSA COVID-19 Clinician Call
June 26 2021
Judy Guzman-Cottrill DOProfessor of Pediatrics
Division of Infectious DiseasesOregon Health amp Science University
Portland Oregon 4
Objectives
1 Briefly discuss recent case series in the journal Pediatrics summarizing 7 adolescents who developed myocarditis after receipt of mRNA COVID-19 vaccination
2 Discuss why this case series was important to quickly publish
5
Conflict disclosure
bull No financial conflicts of interestbull Pediatric infectious disease physicianbull Mother of a 16-year-old boy who is fully vaccinated against COVID
and a 13-year-old girl who received dose 2 last week
6
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
TODAYrsquoS CALL
Myocarditis after COVID-19 mRNA Vaccine
Plus Vaccine QampA
Overview of Myocarditis and Pericarditis Matt Oster MD MPHDirector Childrenrsquos Cardiac Outcomes Research ProgramSibley Heart Center Cardiology Childrenrsquos Healthcare of AtlantaMedical Officer CDC Center on Birth Defects amp Developmental Disabilities Centers for Disease Control and Prevention COVID-19 Response
2
COVID-19 Vaccine Safety Updates Tom Shimabukuro MD MPH MBACaptain US Public Health ServiceDeputy Director Immunization Safety OfficeCenters for Disease Control and Prevention
Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesJudith A Guzman-Cottrill DOProfessor of Pediatrics Division of Infectious DiseasesOregon Health amp Science University School of Medicine
COVID-19 mRNA Vaccines in Adolescents and Young Adults Benefit-Risk DiscussionAmanda Cohn MDChief Medical Officer COVID-19 Task ForceChief Medical Officer National Center for Immunization amp Respiratory DiseasesCaptain US Public Health ServiceCenters for Disease Control and Prevention
Question Use the ldquoQampArdquo Button
Comment Use the ldquoChatrdquo Button
3
Myocarditis and Myopericarditis after COVID-19 Vaccination
A Case SeriesCDCIDSA COVID-19 Clinician Call
June 26 2021
Judy Guzman-Cottrill DOProfessor of Pediatrics
Division of Infectious DiseasesOregon Health amp Science University
Portland Oregon 4
Objectives
1 Briefly discuss recent case series in the journal Pediatrics summarizing 7 adolescents who developed myocarditis after receipt of mRNA COVID-19 vaccination
2 Discuss why this case series was important to quickly publish
5
Conflict disclosure
bull No financial conflicts of interestbull Pediatric infectious disease physicianbull Mother of a 16-year-old boy who is fully vaccinated against COVID
and a 13-year-old girl who received dose 2 last week
6
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Question Use the ldquoQampArdquo Button
Comment Use the ldquoChatrdquo Button
3
Myocarditis and Myopericarditis after COVID-19 Vaccination
A Case SeriesCDCIDSA COVID-19 Clinician Call
June 26 2021
Judy Guzman-Cottrill DOProfessor of Pediatrics
Division of Infectious DiseasesOregon Health amp Science University
Portland Oregon 4
Objectives
1 Briefly discuss recent case series in the journal Pediatrics summarizing 7 adolescents who developed myocarditis after receipt of mRNA COVID-19 vaccination
2 Discuss why this case series was important to quickly publish
5
Conflict disclosure
bull No financial conflicts of interestbull Pediatric infectious disease physicianbull Mother of a 16-year-old boy who is fully vaccinated against COVID
and a 13-year-old girl who received dose 2 last week
6
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Myocarditis and Myopericarditis after COVID-19 Vaccination
A Case SeriesCDCIDSA COVID-19 Clinician Call
June 26 2021
Judy Guzman-Cottrill DOProfessor of Pediatrics
Division of Infectious DiseasesOregon Health amp Science University
Portland Oregon 4
Objectives
1 Briefly discuss recent case series in the journal Pediatrics summarizing 7 adolescents who developed myocarditis after receipt of mRNA COVID-19 vaccination
2 Discuss why this case series was important to quickly publish
5
Conflict disclosure
bull No financial conflicts of interestbull Pediatric infectious disease physicianbull Mother of a 16-year-old boy who is fully vaccinated against COVID
and a 13-year-old girl who received dose 2 last week
6
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Objectives
1 Briefly discuss recent case series in the journal Pediatrics summarizing 7 adolescents who developed myocarditis after receipt of mRNA COVID-19 vaccination
2 Discuss why this case series was important to quickly publish
5
Conflict disclosure
bull No financial conflicts of interestbull Pediatric infectious disease physicianbull Mother of a 16-year-old boy who is fully vaccinated against COVID
and a 13-year-old girl who received dose 2 last week
6
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Conflict disclosure
bull No financial conflicts of interestbull Pediatric infectious disease physicianbull Mother of a 16-year-old boy who is fully vaccinated against COVID
and a 13-year-old girl who received dose 2 last week
6
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Released online ahead of print June 4 2021 7
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
My Co-Authors (5 hospitals)
bull Oregon Health amp Science University Portland ORbull Pediatric Cardiology Infectious Diseases and Radiology
bull Yale University School of Medicine New Haven CTbull Pediatric Cardiology Infectious Diseases and Rheumatology
bull Emory University School of Medicine amp Childrenrsquos Healthcare of Atlanta GAbull Pediatric Cardiology and Infectious Diseases
bull Goryeb Childrenrsquos Hospital Atlantic Health System Morristown NJbull Pediatric Cardiology and Infectious Diseases
bull Spectrum Health Grand Rapids MIbull Adult Interventional Cardiology
8
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Introduction
bull The FDA EUA for Pfizer-BioNTech COVID-19 mRNA vaccine was revised to include children 12 years of age and older on 5102021
bull Around that same time media and case reports suggested a possible correlation of COVID-19 mRNA vaccination and myocarditis
bull United States military bull Israeli cohort identified a male predominancebull 56-year-old man with previous COVID-19 bull 39-year-old man with no history of COVID-19
bull Our case series includes 7 healthy male adolescents with acute symptomatic myocarditis all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccine in April or May 2021
9
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Demographics SymptomsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Age (years) 16 19 17 18 17 16 14
Sex M M M M M M M
Weight (kg) 68 68 71 69 64 71 92
BMI 24 19 21 21 19 22 28
Exposure to COVID-19 No No No No No No No
Post-vaccine symptom onset (days) 2 3 2 2 4 3 2
Hospital LOS (days) 6 2 2 4 5 3 4
ICU LOS (days) 4 None None 4 5 2 2
Chest pain X X X X X X X
Other pain Arm Myalgias Arm Bilateral arm abdominal
Fever X X X X X
Fatigue X X X
Other NV HA WeaknessBilateral arm
numbness paresthesia
N
Palpitations shortness of breath NV
anorexia
Shortness of breath
Shortness of breath
10
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
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Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Diagnostics Time of Admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Troponin 259ngmL (I) 232ngL (T) 555ngmL (I) 109ngmL (T) 32ngmL (T) 066ngmL (T) 221ngmL (I)
BNP 428 pgmL -- 376 pgmL -- 978 pcgmL 149 pcgmL 108 pcgmL
WBC (1000cu mm) 697 869 118 126 163 50 811
ALC (1000cu mm) 169 139 213 23 41 14 105
ANC (1000cu mm) 465 593 746 95 98 28 473
Plt(1000cu mm) 198 208 231 236 297 189 208
AST (uL) 54 29 41 82 150 59 87
ALT (uL) 30 14 33 20 46 22 38
Ferritin (ugL) 70 -- 90 103 347 65 84
CRP (mgdL nl lt 10) 099 67 25 127 181 15 77
ESR (mmhr) 18 13 6 40 38 3 10
11
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Diagnostics Other FindingsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
COVID-19 PCR Neg Neg Neg Neg Neg Neg Neg
COVID-19 spike Ab -- -- Pos Pos Pos Pos --
COVID-19 nucleocapsid Ab Neg -- Neg Neg Neg Neg Neg
Resp pathogen panel PCR Neg Neg Neg Neg Neg Neg Neg
Adenovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR -- Neg sPCR
Enterovirus Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg sPCR
CMV Neg sPCR -- Neg serology Neg sPCR Neg sPCR Neg sPCR Neg serology
EBV -- -- Neg serology Neg sPCR Neg sPCR Neg IgMPos IgG
Neg serology
Other diagnostics
Neg Parvovirus Bartonella and Lyme serology
Neg Parvovirus and Bartonellaserology HHV-6 sPCR
Neg Lyme serology Mycoplasmaand Parvovirus sPCR
Neg Parvovirus IgM pos Parvovirus IgG neg MycoplasmaPCR (throat swab)
Respiratory Panel includes PCR for Adenovirus Coronavirus 229E Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Metapneumovirus (human) RhinovirusEnterovirus Influenza A Influenza B Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4 Respiratory Syncytial Virus Bordetella parapertussis Bordetella pertussis Chlamydophila pneumonia Myocoplasma pneumonia 12
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
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-
Diagnostics CardiographicsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Echocardiogram Normal Normal Borderline basal lateral and basal posterior strain
Normal Normal Normal Mildly depressed RV and LV function
ECG AV dissociation with junction escape rhythm ST elevation
ST elevation (diffuse)
ST elevation (diffuse) T wave abnormality
ST elevation Sinus bradycardia T wave abnormality
ST elevation(diffuse)
ST elevation low voltage of extremity leads
Cardiac MRI LGE myocardial edemaaxillary adenopathy
LGE myocardial edema
LGE myocardial edema
Myocardial edema hyperemia mild mitral regurgitation
LGE no myocardial edema
LGE diffuse myocardial edema
LGE myocardial edema hyperemia
LGE Late gadolinium enhancement
13
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Summary of TherapeuticsPatient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7
Oxygen None None None None None None LFNC - comfort
Vasoactive medications orInotropic support
None None None None None None None
Anti-inflammatory agents and other relevant medications
NSAID (ketorolac)IVIGMethylprednisolonePrednisoneFamotidine
NSAID (ketorolac)Colchicine Aspirin
NSAID (ibuprofen)Famotidine
NSAID (ibuprofen)IVIGMethylprednisolonePrednisone
NSAID (ibuprofen)IVIGMethylprednisolonePrednisoneAspirin
IVIGPrednisone
NSAID (ketorolac naproxen)FamotidineFurosemide
14
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Our Discussion
bull Temporal relationship of clinical myocarditis following second Pfizer-BioNTech COVID-19 vaccine in adolescent males aged 14-19 years of age
bull No patient had acute COVID-19 infectionbull 4 patients had detectable SARS-CoV-2 spike antibodies (component of
vaccine)bull 66 patients had negative SARS-CoV-2 nucleocapsid antibody (suggesting
no prior SARS-CoV-2 infection)bull None of our patients were critically ill and all responded quickly to
treatment however all patients required hospitalization for cardiac monitoring
bull Findings consistent with a known male preponderance of myocarditis
15
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
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wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
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We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
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A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Limitations
bull Compiled cases through personal communications between colleagues rather than a systematic surveillance system
bull Alternative etiologies including idiopathic and other infectious etiologies were not thoroughly excluded
bull There was not a systematic diagnostic evaluation for possible etiologies
bull Cardiac biopsy was not performed on any patients
16
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Objective 2Why was this important to quickly publish
bull Our patientsrsquo presentations were all so similar we were concerned this might be a very early safety signal ndash this was a way to amplify our concerns
bull Early recognition of chest pain elevated troponin and ECG abnormalities following COVID-19 vaccination may prevent invasive procedures (ie cardiac catheterization)
bull To recommend that these patients undergo a comprehensive workup to exclude other causes
bull All authors concluded that the benefits of vaccination significantly exceed possible risks and we encourage following the guidance of the CDC ACIP
bull To highlight importance of promptly reporting all cases to VAERS
17
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
Thank You
18
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
cdcgovcoronavirus
Overview of Myocarditis and PericarditisIDSAJune 26 2021
Matthew Oster MD MPHCDC COVID-19 Vaccine Task Force
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
20
Disclaimer
The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
21
Myocarditis diagnosisProbable
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Elevated troponinbull Electrocardiogram (ECG or EKG) findingsbull Decreased function on echo or MRIbull MRI findings consistent with myocarditis
3 No other identified cause
Confirmed
1 Symptomsbull Chest painpressurediscomfortbull Dyspneashortness of breathbull Palpitations
2 Abnormal testingbull Biopsybull Elevated Troponin AND MRI findings consistent
with myocarditis
3 No other identified cause
Cases with individuals who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed)
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
22
Pericarditis diagnosis
Must have 2 ofbull Chest pain bull Pericardial rub audible by stethoscope bull Abnormal ECG findings (New ST-elevation or PR-depression)bull Pericardial effusion on echocardiogram or MRI
Adler et al Eur Heart J 2015
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
23
Epidemiology of myocarditis Children
bull Annual incidence 08 per 100000bull In 15-18yo 18 per 100000 in 2015-2016
bull 66 malebull Median LOS 61 days
Adultsbull Gradual decrease in incidence with
agebull 76 male
Vasudeva et al American J Cardiology 2021 Kyto et al Heart 2013
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
24
Causes of traditional myocarditis
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
25
Treatment Supportive CareOxygen supplementation even if for comfort
bull Intubation in severe casesFluid resuscitationHeart Failure management
bull Diureticsbull Afterload reductionbull Beta blockers (use in acute setting controversial)bull Inotropesbull Anti-arrhymic medications
Mechanical circulatory supportbull Extracorporeal Membrane Oxygenation (ECMO)bull Ventricular Assist Device (VAD)
Transplant
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
26
Treatment Anti-inflammatory
Non-steroidal Anti-inflammatory Drugs (NSAIDs)bull Mice studies shown to worsen myocardial injury in myocarditis due to
coxsackievirusbull Still often used for mild cases particularly when concern for pericarditis
Intravenous Immunoglobulin (IVIG)bull Also controversial as studies have failed to show benefit particularly in
childrenbull Still often used in many hospitals
Glucocorticoidsbull No good data to support their use yet still commonly usedbull Exception is in giant cell myocarditis (rare)
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
27
Activity Restrictions Risk of sudden death
bull 5-10 of sudden death in adolescents and young adults attributable to myocarditis (typically not previously diagnosed)
Guidelines from American Heart Association and American College of Cardiology
Maron et al JACC 2015Burns et al J Peds X 2020
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
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wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
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HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
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104104
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We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
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105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
28
Outcomes of Classic Myocarditis in Children
Mortality 4-7 during acute illness
Heart Transplant 4-9
Risk factors for worse outcomes in those with known myocarditisbull Late gadolinium enhancement on cardiac MRIbull Tachyarrhythmiasbull Younger agebull Severely decreased function on echocardiogram
bull Higher BNPbull ECMO VAD vasoactive medication use
Ghelani et al Circ Cardiovasc Qual Outcomes 2012Butts et al Pediatric Caridology 2017Sachdeva et al Am J Cardiol2015
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
29
Early reports of myocarditis after mRNA COVID-19 vaccine United States
Marshall et al ndash 7 healthy males 14-19yo within 4 days of 2nd mRNA vaccinebull All with abnormal troponin ECG and MRIbull Treatment with NSAIDs alone in 3 IVIGsteroids in 4bull All discharged to home after 2-6 days in the hospital (median 4)
Rosner et al ndash 5 males 19-39yo within 4 days of 2nd dose of vaccine 1 24yo male 7 days after 1st dosebull All with abnormal troponin and MRI findings varying ECG findings bull Treatment with NSAIDs or colchicine in 4 beta-blockers in 2 steroids in 1bull All discharged to home after 2-4 days in the hospital (median 3)bull Note Spike protein antibodies negative in patient who presented after 1st dose
Marshall et al Pediatrics 2021Rosner et al Circulation 2021Rosner et al also reported a 28yo with myocarditisafter Johnson amp Johnsonrsquos Janssen COVID-19 vaccine
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
30
Early reports of myocarditis after mRNA COVID-19 vaccine International
Larson et al ndash 8 males 22-56yo (4 in US 4 in Italy) 7 within 4 days of dose 2 1 with onset 2 days after dose 1 (had hx of prior SARS-CoV-2 infection)bull All with abnormal troponin echo and MRI 78 with abnormal ECGbull Treatment with NSAIDs or colchicine in 4 steroids in 2 no treatment in 3bull All discharged home with resolution of symptoms and preserved ejection fraction
Israeli Ministry of Health - 148 myocarditis cases occurring within 30 days of mRNA vaccine
bull 27 cases out of ~54 million first dosesbull 121 cases out of ~5 million second doses
bull Mostly in men aged 16-30 (particularly 16-19)bull Most were in the hospital up to 4 daysbull 95 of cases considered mild
Larson et al Circulation 2021httpswwwgovilendepartmentsnews01062021-03
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
31
Summary
Myocarditis is rare but is not a new disease
Treatment largely supportive
Myocarditis after mRNA vaccinesbull Most commonly males lt30 years old within a few days after 2nd dosebull Early data of acute outcomes of myocarditis after mRNA vaccines have
been good but clear evidence of significant inflammation on cMRIbull No long-term data available yet
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
Acknowledgmentsbull CDC Covid-19 Vaccine Task Force Vaccine Safety Teambull Clinical Immunization Safety Assessment Project
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
cdcgovcoronavirus
COVID-19 Vaccine safety updatesInfectious Diseases Society of America (IDSA) COVID-19 Clinician CallJune 26 2021
Tom Shimabukuro MD MPH MBAVaccine Safety TeamCDC COVID-19 Vaccine Task Force
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
-
34
Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC) or the US Food and Drug Administration (FDA) Mention of a product or company name is for identification
purposes only and does not constitute endorsement by CDC or FDA
35
Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
36
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
37
38
Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
ManufacturerReports after
dose 1 Reports after
dose 2Reports after
unknown dose
Pfizer-BioNTech (n=791) 150 563 78
Moderna (n=435) 117 264 54
Total (N=1226) 267 827 132
Includes total preliminary reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis
‒ Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pending
Medical Dictionary for Regulatory Activities httpswwwmeddraorg
39
Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
CharacteristicsDose 1 (n=267)
Dose 2 (n=827)
Median age years (range) 30 (12ndash94) 24 (12ndash87)
Median time to symptom onset days (range) 4 (0ndash61)dagger 3 (0ndash98)dagger
Sex ()Male 176 (66) 655 (79)
Female 88 (33) 165 (20)
Not reportednot available 3 (1) 7 (1)
Includes total reports identified through VAERS database searches for reports with myocarditispericarditis MedDRA codes and pre-screened VAERS reports with signs and symptoms consistent with myocarditispericarditis (and with dose number documented) Follow-up medical record review application of CDC working case definition and adjudication is ongoing or pendingdagger One report of 179-day onset after dose 1 one report of 151-day onset after dose 2 ndash included in counts but not in range
40
05
10152025303540455055606570
12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Prel
imin
ary
repo
rts
Age of reported patient years
Dose 1 Dose 2
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number
(as of Jun 11 2021)
Age truncated at gt50yr Reports of persons gt50yr of age include 70 after Dose 1 119 after Dose 2
41
Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset
(as of Jun 11 2021)
Reports of time to symptom onset truncated at gt29 days Includes 5 reports after Dose 1 56 after Dose 2
0
20
40
60
80
100
120
140
160
180
200
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Prel
imin
ary
repo
rts
Time from vaccination to symptom onset days
Dose 1 Dose 2
42
416
117
295 310
81
0
50
100
150
200
250
300
350
400
450
Chest pain Dyspnea ST or -T wave change Elevated cardiac enzymes Abnormal echocardiography imaging
Num
ber o
f ide
ntifi
ed re
port
s
Symptom or diagnostic findings
Symptoms and diagnostic findings of preliminary myocarditispericarditis reports after mRNA COVID-19
vaccination under review limited to le29 years old (N=484)(data thru Jun 11 2021)
43
Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
484 total preliminary reports 323 have met CDC working
case definition of myocarditis or pericarditis (or both) 148 are under review
Of 323 meeting case definition 309 were hospitalized
‒ 295 discharged
bull 218 (79) known to have recovered from symptoms at time of report
‒ 9 still hospitalized (2 in ICU)
‒ 5 without outcome data
14 were not hospitalized (seen in emergency dept urgent care outpatient clinic not specified)
44
Preliminary myocarditispericarditis reports to VAERS following dose 2mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 0ndash2 19 2039871 0ndash4 128
18ndash24 yrs 5237262 1ndash6 23 4337287 1ndash8 219
25ndash29 yrs 4151975 0ndash5 7 3625574 1ndash7 59
30ndash39 yrs 9356296 2ndash18 11 8311301 2ndash16 61
40ndash49 yrs 9927773 2ndash19 18 8577766 2ndash16 34
50ndash64 yrs 18696450 4ndash36 18 16255927 3ndash31 18
65+ yrs 21708975 4ndash42 10 18041547 3ndash35 11
Not reported mdash mdash 1 mdash mdash 8 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
45
Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
Overall reportingrate per million doses
Reporting rate in femalesper million doses
Reporting rate in malesper million doses
Age groups All doses Dose 1 Dose 2 All doses Dose 1 Dose 2 All doses Dose 1 Dose 2
12-17 yrs 181 53 370 42 11 91 324 98 667
18-24 yrs 159 48 284 36 15 55 307 87 563
25-29 yrs 67 25 108 20 08 26 122 45 204
30-39 yrs 42 17 56 18 14 18 69 20 100
40-49 yrs 27 09 38 20 09 28 35 10 51
50-64 yrs 17 10 20 16 10 18 19 10 23
65+ yrs 11 07 13 11 06 12 12 07 14
Myocarditispericarditis reports per million mRNA vaccine doses administered by sex and dose number with no restrictions on post-vaccination observation time
46
VSDVaccineSafetyDatalink
9 participating integrated healthcare organizations
Data on over 12 million persons per year
47
VSD Rapid Cycle Analysis (RCA) safety monitoring
Near real-time sequential (ie weekly) monitoring as data become available Monitors a limited set of prespecified vaccine safety outcomes A public health surveillance activity not the same as an
epidemiologic study Designed to detect statistically significant associations and statistical
signals (values above specified statistical thresholds) which do not necessarily indicate a safety problem Statistical signals detected through RCA require further evaluation
48
COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
4551160total doses
5781728total doses
49
COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
Pfizer-BioNTech doses 12ndash15-year-olds
‒ 176987 first doses‒ 66546 second doses
16ndash17-year-olds‒ 127665 first doses‒ 101938 second doses
50
VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar date ne=not estimable
Pre-specified outcome eventEvents in risk
intervalAdj
Rate Ratio 95 CI SignalAcute disseminated encephalomyelitis 2 007 - ne noAcute myocardial infarction 578 099 085 - 115 noAppendicitis 691 080 070 - 090 noBellrsquos palsy 493 097 083 - 115 noCerebral venous sinus thrombosis 5 115 023 - 667 noDisseminated intravascular coagulation 28 065 035 - 120 noEncephalitis myelitis encephalomyelitis 15 094 035 - 277 noGuillain-Barreacute syndrome 8 057 016 - 215 noStroke hemorrhagic 227 081 064 - 103 noStroke ischemic 1009 098 087 - 110 noImmune thrombocytopenia 45 103 059 - 185 noKawasaki disease 0 000 000 - 260 noMyocarditis pericarditis 75 107 070 - 167 noSeizures 266 103 082 - 130 noTransverse myelitis 3 188 017 - 5581 noThrombotic thrombocytopenic purpura 5 139 027 - 802 noThrombosis with thrombocytopenia syndrome (TTS) 66 079 052 - 120 noVenous thromboembolism 579 107 092 - 125 noPulmonary embolism 484 099 084 - 118 no
(thru Jun 12 2021)
51
Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
(thru Jun 5 2021)
n=3 events in comparison window
(22ndash42 days)
Most likely clusters‒ Days 0ndash5‒ Days 0ndash3‒ Days 0ndash6
All have a p-value lt0000001 Parameters for the scan
‒ Includes days 0ndash56‒ Scans all possible windows of
length 1ndash28 days
n=29 events in the 0-21 days
post-vaccination
52
VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
Adjusted for VSD site 5-year age group sex raceethnicity and calendar datedagger Moderna COVID-19 Vaccine is not authorized in persons aged lt18 yearsDagger ne=not estimable no events in comparison interval (22ndash42 days after final dose)
Vaccine (dose )Events in risk
intervalAdj
Rate ratio 95 CIAny mRNA (both doses) 22 100 29ndash465
Any mRNA (dose 1) 4 62 09ndash698Any mRNA (dose 2) 18 108 32ndash490
Pfizer-BioNTech (both doses) 7 24 04ndash249Pfizer-BioNTech (dose 1) 0 0 0ndash204Pfizer-BioNTech (dose 2) 7 60 11ndash536
Moderna (both doses)dagger 15 69ndashneModerna (dose 1) 4 21ndashneModerna (dose 2) 11 66ndashne
(thru Jun 5 2021)
53
Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
Vaccine(s) (dose ) CasesDoses admin
Rate per million doses
(95 CI)mRNA (both doses) 26 3418443 8 (53ndash118)
mRNA (dose 1) 8 1879585 44 (19ndash88)
mRNA (dose 2) 18 1538858 126 (75ndash199)
Pfizer-BioNTech (dose 1) 3 1211080 26 (05ndash77)
Pfizer-BioNTech (dose 2) 7 958721 80 (32ndash165)
Moderna (dose 1) 5 668505 75 (24ndash176)
Moderna (dose 2) 11 580137 198 (99ndash355)
(thru Jun 5 2021)
54
Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
Care and status n ()Highest level of care received
Outpatient 1 (34)Emergency department 4 (138)Inpatient hospitalization 22 (759)Intensive care unit (ICU) 2 (57)
Median length of hospital stay (days range) 1 (0ndash13)Discharged to home at time of chart review 29 (100)Follow-up visit noted at time of chart review 27 (931)
Follow-up qualitative summaryCurrent symptoms Nearly all follow-up visit notes indicated resolution of symptoms at the time of follow-up Of those that had follow-up ECGecho lab testing most had returned to normal or baseline
Ongoing treatmentplan Most follow-up visit notes indicate tapering of some medications (NSAIDS prednisone etc) Notes indicated maintenance of colchicine and activity limitations for 3ndash6 months
3 of the 29 cases (103) had a history of COVID-19 infection
55
Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
(thru Jun 5 2021)
Product (dose)Femalecases
Female ratesper million doses
(95 CI)Malecases
Male ratesper million doses
(95 CI)
Any mRNA (both doses) 6 32 (12ndash69) 26 169 (110ndash248)Any mRNA (dose 1) 2 19 (02ndash70) 4 47 (13ndash120)Any mRNA (dose 2) 4 47 (13ndash120) 22 320 (201ndash485)
Pfizer-BioNTech (both doses) 1 08 (00ndash47) 11 111 (55ndash198)Pfizer-BioNTech (dose 1) 1 15 (00ndash85) 1 18 (00ndash100)Pfizer-BioNTech (dose 2) 0 ( ndash ) 10 230 (110ndash423)
Moderna (both doses) 5 71 (23ndash166) 15 275 (154ndash454)Moderna (dose 1) 1 27 (01ndash149) 3 102 (21ndash299)Moderna (dose 2) 4 122 (33ndash312) 12 477 (246ndash833)
56
Summary
57
Summary Analysis of VAERS preliminary reports of myocarditispericarditis is in progress including
follow-up to obtain medical records complete reviews apply CDC working case definition and adjudicate cases
Preliminary VAERS findings suggest‒ Median age of reported patients is younger for reports after dose 2 vs dose 1‒ Symptom onset clusters within the week following vaccination (mostly within 4 days)‒ Predominance of male patients in younger age groups especially after dose 2‒ Observed reports gt expected cases especially after dose 2 in younger age groups
Early VSD data for myocarditispericarditis in 12ndash39-year-olds also suggest‒ More cases after mRNA COVID-19 vaccination with dose 2 vs dose 1‒ Rate of 126 cases per million 2nd doses of any mRNA vaccine in the 21 days following vaccination
bull Rates appear higher in males vs females‒ Clustering of myocarditispericarditis within the week following vaccination (most likely 0ndash5 days)
Available outcome data indicate that patients generally recover from symptoms and do well
58
Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
Continue monitoring in VAERS‒ Follow-up to obtain medical records conduct case reviews apply CDC
working case definition and adjudicate case reports‒ Surveillance review focusing on myocarditis and myopericarditis to describe
epidemiology and characterize clinical features of cases is in progress
Continue monitoring and assessment in VSD‒ Quantify risk and characterize clinical features of cases
Conduct follow-up on vaccine-associated cases to assess longer-term outcomes (ie at 3ndash6 months)
59
CDC educational materials
CDC httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml and httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtml
60
How to report an adverse event to VAERS
Go to vaershhsgov
Submit a report online
For helpCall 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
Please send records to VAERS ASAP if contacted and asked
‒ HIPAA permits reporting of protected health information to public health authorities including CDC and FDA
61
Acknowledgments
Centers for Disease Control and PreventionCOVID-19 Vaccine Task ForceVaccine Safety TeamImmunization Safety OfficeDivision of Healthcare Quality PromotionClinical Immunization Safety Assessment ProjectVaccine Safety Datalink
Food and Drug AdministrationCenter for Biologics Evaluation and Research
We wish to acknowledge the contributions of investigators from the following organizations
62
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Thank you
For more information contact CDC1-800-CDC-INFO (232-4636)TTY 1-888-232-6348 wwwcdcgov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention
Extra slides
65
Timeline US adolescent COVID-19 vaccination December 2020 FDA issues Emergency Use Authorizations (EUAs) for two COVID-19 vaccines
‒ Pfizer-BioNTech COVID-19 vaccine for persons aged ge16 years‒ Moderna COVID-19 vaccine for persons aged ge18 years
December 2020 CDC publishes ACIP interim recommendations for use of Pfizer-BioNTech and Moderna COVID-19 vaccines for age groups indicated in EUAsdagger
February 2021 FDA issues EUA for Janssen COVID-19 vaccines for persons aged ge18 years
March 2021 CDC published ACIP interim recommendations for use of Janssen COVID-19 vaccine for age group indicated in EUAdagger
May 2021‒ FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12ndash
15 years
‒ ACIP publishes interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12ndash15 yearsdagger
FDA COVID-19 Vaccines httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccinesdagger CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19html
66
Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
67
httpcdcgovvsafe
Smartphone-based active safety monitoring
68
Overview of v-safe monitoring of Pfizer-BioNTechCOVID-19 vaccine for younger adolescents
On May 11 2021 v-safe age limits expanded to allow registration down to 12 years of age at dose 1 As of June 13 for persons age 12ndash15 years after Pfizer-BioNTech
COVID-19 vaccination‒ 57126 with at least one health check-in during days 0ndash7 after dose 1‒ 15988 with at least one health check-in during days 0ndash7 after dose 2
69
V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
70
V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds
(data thru Jun 13 2021)
Includes participants who completed at least one survey in the first week after dose 1 of Pfizer-BioNTech COVID-19 vaccine
Dose 1 Pfizer-BioNTechCOVID-19 vaccination
Dose 2 Pfizer-BioNTechCOVID-19 vaccination
Medical care in emergency depthospital12-15 years 0116-25 years 01
Medical care in emergency depthospital12-15 years 0216-25 years 02
71
+ co-managed byCDC and FDA
Vaccine Adverse Event Reporting System
httpvaershhsgov
VAERS is the nationrsquos early warning system for vaccine safety
72
VAERS
key strengths Rapidly detects potential
safety problems Can detect rare adverse
events
key limitations Inconsistent quality and
completeness of information Reporting biases Generally cannot determine
cause and effect
VAERS accepts all reports from everyone regardless of the plausibility of the vaccine causing the event or the clinical seriousness of the event
73
Source Shimabukuro et al Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS) Vaccine 2015 Aug 2633(36)4398-405
Whatrsquos in VAERS
Does not necessarily mean
vaccination caused a health problem
74
Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
Ages NCrude reporting rate (per million doses)
Non-seriousadverse events ()
Serious adverse eventsDaggersect ()
12ndash15 years old 2540 422 2396 (943) 144 (57)
16ndash25 years olddagger
(for comparison) 12759 592 11969 (938) 790 (62)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Based on the Code of Federal Regulations if one of the following is reported death life-threatening illness hospitalization or prolongation of hospitalization permanent disability congenital anomaly or birth defectsect Includes 1 report of death in the 12ndash15-year-old age group and 18 reports of death in the 16ndash25-year-old age group
12ndash15 years old ~60 million doses administered (May 10 thru June 11 2021)
16ndash25 years old ~216 million doses administered (December 14 2020 thru June 11 2021)
75
Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
Data as of June 14 2021 for reports with vaccination date and receipt date May 10 through June 11 2021dagger Data as of June 14 2021 for reports with vaccination date and receipt date December 14 2020 through June 11 2021Dagger Adverse events are not mutually exclusive
Adverse eventDagger n ()Dizziness 618 (243)Syncope 446 (176)Nausea 308 (121)
Headache 281 (111)Vomiting 221 (87)
Pallor 218 (86)Loss of consciousness 217 (85)
Pyrexia (fever) 215 (85)Hyperhidrosis 211 (83)
Fatigue 182 (72)
Adverse eventDagger n ()Dizziness 2832 (222)Headache 2197 (172)
Nausea 1955 (153)Pyrexia (fever) 1948 (153)
Fatigue 1689 (132)Chills 1609 (126)Pain 1560 (122)
Syncope 1257 (99)Hyperhidrosis 946 (74)
Vomiting 918 (72)
12ndash15 years old (N= 2540) 16ndash25 years olddagger (N= 12759)(for comparison)
12ndash15 years old ~60 million doses administered (May 10 thru Jun 11 2021) 16ndash25 years old ~216 million doses administered (December 14 2020 thru Jun 11 2021)
76
CDC working case definition for acute myocarditis
77
CDC working case definition for acute pericarditis
78
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MaleDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 1ndash13 4 3569239 2ndash21 32
18ndash24 yrs 6830706 2ndash23 9 5863268 3ndash34 47
25ndash29 yrs 5198356 2ndash18 3 4685036 3ndash27 18
30ndash39 yrs 11505068 7ndash66 15 10391499 6ndash60 17
40ndash49 yrs 11996507 7ndash69 9 10513258 6ndash60 8
50ndash64 yrs 21957007 13ndash126 22 19270825 11ndash111 18
65+ yrs 24795212 14ndash143 13 20473779 12ndash118 15
Not reported mdash mdash 2 mdash mdash 4 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
79
Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 3777097 0ndash4 3 3569239 1ndash7 27
18ndash24 yrs 6830706 1ndash8 6 5863268 1ndash11 41
25ndash29 yrs 5198356 1ndash6 2 4685036 1ndash9 14
30ndash39 yrs 11505068 1ndash13 8 10391499 2ndash20 14
40ndash49 yrs 11996507 1ndash14 1 10513258 2ndash20 5
50ndash64 yrs 21957007 2ndash25 16 19270825 4ndash37 10
65+ yrs 24795212 2ndash25 8 20473779 4ndash39 8
Not reported mdash mdash 2 mdash mdash 2 Assumes a 7-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 6 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
80
Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
Age groups
Females MalesDoses admin Expecteddagger Observed
Doses admin Expecteddagger Observed
12ndash17 yrs 2189726 1ndash7 20 2039871 1ndash12 132
18ndash24 yrs 5237262 2ndash18 27 4337287 2ndash25 233
25ndash29 yrs 4151975 1ndash15 11 3625574 2ndash21 69
30ndash39 yrs 9356296 5ndash54 14 8311301 5ndash48 71
40ndash49 yrs 9927773 6ndash57 23 8577766 5ndash49 40
50ndash64 yrs 18696450 11ndash108 25 16255927 9ndash94 34
65+ yrs 21708975 12ndash125 17 18041547 10ndash104 16
Not reported mdash mdash 1 mdash mdash 9 Assumes a 21-day post-vaccination observation window (ie symptom onset from day of vaccination through Day 20 after vaccination)dagger Based on Gubernot et al US Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines Vaccine 2021 May 14S0264-410X(21)00578-8 Expected counts among females 12ndash29 years adjusted for lower prevalence relative to males by factor of 17 (Fairweather D et al Curr Probl Cardiol 201338(1)7-46)
cdcgovcoronavirus
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussion
Dr Megan Wallace and Dr Sara OliverACIP MeetingJune 23 2021
COVID-19 vaccines are recommended for persons 12 years of age and older in the United States under FDArsquos Emergency Use Authorization
Current COVID-19 mRNA vaccine policy
82
httpscovidcdcgovcovid-data-trackerdemographics
Adolescents and young adults have the highest COVID-19 incidence rates
COVID-19 Incidence Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
0 200 400 600 800 1000 1200
12-17 Years
18-24 Years
25-29 Years
30-49 Years
50-64 Years
65+ Years
COVID-19 Incidence Rate per 100000 Population
Female
Male
83
Since beginning of pandemic at least 77
million COVID-19 cases have been reported among persons aged
12ndash29 years
httpsgiscdcgovgraspCOVIDNetCOVID19_3html
COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
84
00
10
20
30
40
50
60
70
80
90Ra
tes
per 1
000
00 p
opul
atio
n
25-29 years
18-24 years
12-17 years
Weekly COVID-19-associated hospitalization rates by age groupCOVID-NET March 7 2020 ndash May 22 2021
httpscovidcdcgovcovid-data-trackerdemographics
COVID-19-associated deaths continue to occur in adolescents and young adults
COVID-19 Mortality Rate per 100000 Population by Age Group and SexApril 1 2021 ndash June 11 2021
00 01 02 03 04 05 06 07 08 09 10
12-17 Years
18-24 Years
25-29 Years
COVID-19 Mortality Rate per 100000 Population
Female
Male
85
Since beginning of pandemic
2767 COVID-19 deaths have been reported
among persons aged 12-29 years
316 deaths reported since April 1 2021
Post-COVID conditions can occur after COVID-19
1Buonsenso et al Acta Paediatrica (2021)2Walsh-Messinger et al medRXiv (2020)
86
No standardized definition but generally new or persisting symptoms from acute infection or exacerbation of a chronic condition ge4 weeks after SARS-CoV-2 infection Reported after infections ranging from asymptomatic to severe Limited data in adolescentsyoung adults but recent cross-sectional studies have
shown evidence of new or persisting COVID symptoms in this age group12
ndash Up to one-half of study participants had symptoms 1 month post-diagnosisndash Symptoms reported include fatigue insomnia rhinorrhea muscle pain headache
lack of concentration exercise intolerance dyspnea chest pain
Severe hyperinflammatory syndrome occurring 2ndash6 weeks after acute SARS-CoV-2 infection among persons lt21 years old resulting in a wide range of manifestations and complicationsndash 60ndash70 of patients are admitted to intensive care 1ndash2 die12
4018 MIS-C cases have been reported to national surveillance as of June 2 20213
ndash Estimated incidence of 1 MIS-C case in 3200 SARS-CoV-2 infections4
ndash 36 of cases in persons aged 12ndash20 yearsndash 62 of reported cases have occurred in children who are HispanicLatino or Black
Non-Hispanic
Multisystem Inflammatory Syndrome in Children (MIS-C)
1 Feldstein LR Tenforde MW Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 JAMA 2021325(11)1074-1087 doi101001jama202120912 Belay ED Abrams J Oster ME et al Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic [published online ahead of print 2021 Apr 6] JAMA Pediatr 2021e210630 doi101001jamapediatrics202106303 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States httpswwwcdcgovmis-ccasesindexhtml4 Payne et al JAMA Netw Open 20214(6)e2116420 doi101001jamanetworkopen202116420 87
1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1
ndash 37 (23) with abnormal MRI findingsndash However 24 (65) of 37 had normal lab findings and no symptomsndash Another study suggested some MRI findings may be related to remodeling from athletic training2
Retrospective study mdash children with acute myocarditis treated at a single center from 2018ndash20203
ndash 27 children lt18 years of age identifiedndash 727 (26) had evidence of prior SAR-CoV-2 infection or exposure
bull 6 ultimately diagnosed with MIS-Cndash Individuals with myocarditisMIS-C related to SARS-CoV-2 had better clinical course
bull None diagnosed with acute fulminant myocarditisbull Shorter duration of inotropic drug support and ICU staybull Did not require mechanical respiratory support
Myocarditis and COVID-19
881Daniels CJ et al JAMA Cardiol Pub online May 27 2021 doi101001jamacardio20212065 2Clark DE et al Circulation 2021143(6) 3Vukomanovic et al PIDJ202140(5)e173-e178
COVID-19 incidence hospitalization and mortality rates are decreasing overallndash Variants continue to spread and scenarios exist in which cases increase in fallndash Adolescents are growing proportion of cases given vaccine coverage among adults
Post COVID-19 conditions also impact adolescents and young adultsndash 4018 MIS-C cases have been reported to national surveillance
Myocarditis is a disease marked by inflammation of the heart musclendash Risk factors include younger age and male sexndash Can occur with SARS-CoV-2 infection
Myocarditis after mRNA vaccines noted with highest frequency in males aged 12ndash29 years following 2nd dosendash Early outcomes have been encouraging but no long-term data available yet
Summary
89
Risk after COVID-19 mRNA
vaccines in adolescents and
young adults
COVID-19 mRNA vaccines in adolescents and young adults
90
Benefits of COVID-19 mRNA
vaccines in adolescents and
young adults
91
Potential harms of the mRNA COVID-19 vaccines After dose 2
133 million vaccine 2nd doses administeredand 636 reported myocarditis cases as of June 11 2021
ndash Additional potential myocarditis cases under review
Females Males
Age group Casessect Doses admin Reporting ratedagger Casessect Doses admin Reporting ratedagger
12-17 years old 19 2189726 868 128 2039871 6275
18-24 years old 23 5237262 439 219 4337287 5049
25-29 years old 7 4151975 169 59 3625574 1627
30-39 years old 11 9356296 118 61 8311301 734
40-49 years old 18 9927773 181 34 8577766 396
50-64 years old 18 18696450 096 18 16255927 111
65+ years old 10 21708975 046 11 18041547 061sect Cases reported through VAERS using a 7-day risk window Source of doses administered httpscovidcdcgovcovid-data-trackervaccinations Some age- and sex-specific doses administered data were imputeddaggerReporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered
12 ndash 1718 ndash 2425 ndash 2930 ndash 3940 ndash 4950 ndash 64
65+
Benefits and risks after dose 2 by age group
For every million doses of mRNA vaccine given with current US exposure risk1
657 Hospitalizations Prevented
1 Based on hospitalization rates from COVID-NET as of May 22nd BenefitRisk calculated over 120 days 92
0500100015002000 0 500 1000 1500 2000
COVID-19-Associated Hospitalizations Prevented
Cases of Myocarditis
31459027
Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
Females 18ndash24 Years Males 18ndash24 Years
93
14000 COVID-19 cases prevented
1127 hospitalizations prevented
93 ICU admissions prevented
13 deaths prevented
4ndash5 myocarditis cases
12000 COVID-19 cases prevented
530 hospitalizations prevented
127 ICU admissions prevented
3 deaths prevented
45ndash56 myocarditis cases
Hospitalizations ICU admissions and deaths based on data for week of May 22 2021
Benefit-risk analyses
94
Population Level Considerations
No alternatives to mRNA vaccines for the foreseeable future in adolescents Vaccination of students offers an added layer of protection against COVID-19 and
can be an important tool to return to lsquonormalrsquo Higher levels of vaccination coverage can lead to less community transmission
which can protect against development and circulation of emerging variants Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1
ndash Potential changes in vaccine policy or anything that would impact vaccination coverage for adolescentsyoung adults may disproportionately impact those groups with highest rates of poor COVID-19 outcomes
1 httpscovidcdcgovcovid-data-trackerdemographics
Direct benefit-risk assessment shows positive balance for all age and sex groupsndash Considers individual benefits of vaccination vs individual risksndash Benefits are likely an underestimate
bull Analysis was performed using reported rates of cases and hospitalizationsbull Likely represent only a fraction of the true cases that have occurred in the population
ndash Still uncertainty in rates of myocarditis after mRNA vaccinesbull Not all cases are verified and crude rates were used
Balance of risks and benefits varies by age and sexndash Balance could change with increasing or decreasing incidence
Limited data currently on risk of myocarditis in 12ndash15 year old populationndash Due to timing of recommendations limited number of 2nd doses given
Benefit-risk interpretations and limitations
95
Clinical Considerations
COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
97
bull Initial presentations are reassuring however continued monitoring of cases clinical course and long-term outcomes of myocarditis after mRNA vaccines will be important
bull Need to follow the benefit-risk balance as we learn more around myocarditis as well as updates to epidemiology (cases variants etc)
bull Currently the benefits still clearly outweigh the risks for COVID-19 vaccination in adolescents and young adults
Vaccine considerations in people with a history of myocarditis or pericarditis
Scenario RecommendationPericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine
Pericarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Proceed with a 2nd dose of mRNA COVID-19 vaccine after resolution of symptoms Discuss with patient guardian and clinical team
Myocarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine if heart has recovered
Myocarditis after 1st dose of an mRNA COVID-19 vaccine but prior to 2nd dose
Defer 2nd dose of mRNA COVID-19 vaccine until more information is knownHowever if heart has recovered could consider proceeding with 2nd dose under certain circumstances Discuss with patient guardian and clinical team
98
Stephen Hadler Gayle Langley Julia Gargano Jessica MacNeil Heather Scobie Danielle Moulia Mary Chamberland Nicole Reisman Jack Gersten Eddie Shanley Hannah Rosenblum
COVID-19 Vaccine Task Force Vaccine Safety Team Immunization team Epi Task Force
ndash MIS-C unitndash COVID-NET Data Analytics and Visualization Task
Force Division of Healthcare Quality Promotion Respiratory Viruses Branch
Acknowledgements
99
QampA and Discussion
100
Links and Resources bull Slide 1 ndash Call recording wwwidsocietyorgcliniciancallsbull Slide 30 - Larson et al Circulation 2021 httpswwwgovilendepartmentsnews01062021-03bull Slide 36 - VAERS - httpvaershhsgovbull Slide 37 - More information about clinical consults available at httpswwwcdcgovvaccinesafetyactivitiescisahtmlbull Slide 38 - CDC Medical Dictionary for Regulatory Activities httpswwwmeddraorgbull Slide 59 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetymyocarditishtml
httpswwwcdcgovvaccinescovid-19clinical-considerationsmyocarditishtmlbull Slide 60 - How to report to VAERS
VAERS - httpvaershhsgovFor help Call 1-800-822-7967Email infoVAERSorgvideo instructions httpsyoutubesbCWhcQADFE
bull Slide 62 - httpswwwcdcgovcoronavirus2019-ncovvaccinessafetyhtmlbull Slide 65 - FDA httpswwwfdagovemergency-preparedness-and-responsecoronavirus-disease-2019-covid-19covid-19-vaccines
CDC COVID-19 ACIP Vaccine Recommendations httpswwwcdcgovvaccineshcpacip-recsvacc-specificcovid-19htmlbull Slide 67 - httpcdcgovvsafebull Slides 83 85 and 94 - httpscovidcdcgovcovid-data-trackerdemographicsbull Slide 84 - httpsgiscdcgovgraspCOVIDNetCOVID19_3htmlbull Slide 87 - Health Department-Reported Cases of MIS-C in the United States httpswwwcdcgovmis-ccasesindexhtmlbull Slide 91 - Source of doses administered httpscovidcdcgovcovid-data-trackervaccinationsbull Slide 102 - httpswwwidsocietyorgcovid-19-real-time-learning-network 101
An online community bringing together information and opportunities for discussion on latest research guidelines tools and resources from a
variety of medical subspecialties around the world
Specialty Society Collaborators
American Academy of Family PhysiciansAmerican Academy of Pediatrics
American College of Emergency PhysiciansAmerican College of Physicians
American Geriatrics SocietyAmerican Thoracic Society
Pediatric Infectious Diseases Society Society for Critical Care Medicine
Society for Healthcare Epidemiology of AmericaSociety of Hospital Medicine
Society of Infectious Diseases Pharmacists
wwwCOVID19LearningNetworkorgRealTimeCOVID19RealTimeCOVID19
102
cdcgovcoronavirus
CDC-IDSA Partnership Clinical Management Call Support
FOR WHOM- Clinicians who have questions about the clinical
management of COVID-19
WHAT- Calls from clinicians will be triaged by CDC to a group of
IDSA volunteer clinicians for peer-to-peer support
HOW- Clinicians may call the main CDC information line at 800-
CDC-INFO (800-232-4636)- To submit your question in writing go to
wwwcdcgovcdc-info and click on Contact Form
TM
Attend Learn amp CollaborateAdvancing Science Improving Care
Virtual Conferenceidweekorg
Save the Date
Important Datesbull Registration is Open bull Abstract Submission Deadline ndash June 9bull Case Submission Deadline ndash June 9
Sept 29 ndash Oct 3 2021
104104
Continue the conversation on Twitter
RealTimeCOVID19RealTimeCOVID19
We want to hear from youPlease complete the post-call surveyClinician calls are now twice a month
Updated Summer Schedule July 17July 31
August 14August 28
A recording of this call will be posted Monday at wwwidsocietyorgcliniciancalls
-- library of all past calls available --
Contact UsDana Wollins (dwollinsidsocietyorg)Deirdre Lewis (dlewisidsocietyorg)
105
- CDCIDSA COVID-19 Clinician CallJune 26 2021
- TODAYrsquoS CALLMyocarditis after COVID-19 mRNA Vaccine Plus Vaccine QampA
- Slide Number 3
- Myocarditis and Myopericarditis after COVID-19 Vaccination A Case SeriesCDCIDSA COVID-19 Clinician CallJune 26 2021
- Objectives
- Conflict disclosure
- Slide Number 7
- My Co-Authors (5 hospitals)
- Introduction
- Demographics Symptoms
- Diagnostics Time of Admission
- Diagnostics Other Findings
- Diagnostics Cardiographics
- Summary of Therapeutics
- Our Discussion
- Limitations
- Objective 2Why was this important to quickly publish
- Thank You
- Overview of Myocarditis and PericarditisIDSAJune 26 2021
- Disclaimer
- Myocarditis diagnosis
- Pericarditis diagnosis
- Epidemiology of myocarditis
- Causes of traditional myocarditis
- Treatment Supportive Care
- Treatment Anti-inflammatory
- Activity Restrictions
- Outcomes of Classic Myocarditis in Children
- Early reports of myocarditis after mRNA COVID-19 vaccine United States
- Early reports of myocarditis after mRNA COVID-19 vaccine International
- Summary
- Slide Number 32
- COVID-19 Vaccine safety updates Infectious Diseases Society of America (IDSA) COVID-19 Clinician Call June 26 2021
- Disclaimer
- Myocarditis and pericarditis following mRNA COVID-19 vaccination in the United States
- Slide Number 36
- Slide Number 37
- Preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination by dose number (after ~300 million mRNA doses administered data thru Jun 11 2021)
- Characteristics of preliminary myocarditispericarditis reports to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by age and dose number(as of Jun 11 2021)
- Preliminary reports of myocarditispericarditis to VAERS after mRNA COVID-19 vaccination by dose number and time to symptom onset(as of Jun 11 2021)
- Slide Number 42
- Care and outcomes of preliminary myocarditispericarditis cases reported to VAERS after mRNA COVID-19 vaccination in persons lt29 years old (N=484) (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis crude reporting rates to VAERS following mRNA COVID-19 vaccination (data thru Jun 11 2021)
- Slide Number 46
- VSD Rapid Cycle Analysis (RCA) safety monitoring
- COVID-19 vaccine doses administered in the VSD (thru Jun 12 2021)
- COVID-19 vaccine doses administered by age group in the VSD (thru Jun 12 2021)
- VSD Rapid Cycle Analysis Outcome events in the 21-day risk interval after either dose of any mRNA vaccine compared with outcome events in vaccinated comparators on the same calendar days
- Chart confirmed myocarditispericarditis cases in VSD by day of symptom onset since most recent mRNA COVID-19 vaccination 12ndash39-year-olds
- VSD age-stratified analysis Chart confirmed myocarditispericarditis events in 12ndash39-year-olds in the 7-day risk interval compared with events in vaccinated comparators on the same calendar days
- Myocarditispericarditis chart confirmed rates in VSD in 21-day risk interval 12ndash39-year-olds
- Care and status of chart confirmed myocarditispericarditis cases in VSD within 0ndash21 days following mRNA COVID-19 vaccination (N=29)
- Myocarditispericarditis rates based on ICD-10 coded cases in VSD in 21-day risk interval ages 12ndash39 years old
- Summary
- Summary
- Next steps for assessing myocarditispericarditis following mRNA COVID-19 vaccination
- CDC educational materials
- How to report an adverse event to VAERS
- Acknowledgments
- Slide Number 62
- Slide Number 63
- Slide Number 64
- Timeline US adolescent COVID-19 vaccination
- Early safety data of Pfizer-BioNTech vaccination in persons aged 12ndash15 years old
- Slide Number 67
- Overview of v-safe monitoring of Pfizer-BioNTech COVID-19 vaccine for younger adolescents
- V-safe Top solicited reactions reported at least once in days 0ndash7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds(data thru Jun 13 2021)
- V-safe Health Impact Events reported at least once in days 0-7 after vaccination with Pfizer-BioNTech in 12ndash15-year-olds vs 16ndash25-year-olds (data thru Jun 13 2021)
- Slide Number 71
- VAERS
- Whatrsquos in VAERS
- Reports to VAERS after Pfizer-BioNTech COVID-19 vaccination persons aged 12ndash15 years vs 16ndash25 years (data thru Jun 11 2021)
- Most commonly reported adverse events to VAERS after Pfizer-BioNTech COVID-19 vaccination (data thru Jun 11 2021)
- CDC working case definition for acute myocarditis
- CDC working case definition for acute pericarditis
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 1 mRNA COVID-19 vaccination Exp vs Obs using 7-day risk window (data thru Jun 11 2021)
- Preliminary myocarditispericarditis reports to VAERS following dose 2 mRNA COVID-19 vaccination Exp vs Obs using 21-day risk window (data thru Jun 11 2021)
- Slide Number 81
- Current COVID-19 mRNA vaccine policy
- Adolescents and young adults have the highest COVID-19 incidence rates
- COVID-19-associated hospitalization rates have remained stable in adolescents and young adults
- COVID-19-associated deaths continue to occur in adolescents and young adults
- Post-COVID conditions can occur after COVID-19
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Myocarditis and COVID-19
- Summary
- COVID-19 mRNA vaccines in adolescents and young adults
- Potential harms of the mRNA COVID-19 vaccines After dose 2
- Benefits and risks after dose 2 by age group
- Predicted cases prevented vs myocarditis cases for every million second dose vaccinations over 120 days
- Benefit-risk analyses
- Benefit-risk interpretations and limitations
- Clinical Considerations
- COVID-19 mRNA vaccines in adolescents and young adults Benefit-risk discussionWork Group Interpretation
- Vaccine considerations in people with a history of myocarditis or pericarditis
- Acknowledgements
- Links and Resources
- Slide Number 102
- CDC-IDSA Partnership Clinical Management Call Support
- Slide Number 104
- Continue the conversation on TwitterRealTimeCOVID19RealTimeCOVID19
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