Oct 29, 2020CDC Webinar Series

John Conly CM MD CCFP FRCPC FCAHS FAMMI FACP FIDSA FSHEAProfessor of Medicine, Microbiology, Immunology & Infectious Diseases Pathology & Laboratory MedicineMedical Director IPC, Calgary and AreaSynder Institute for Chronic Diseases and O’Brien Institute for Public Health, University of Calgary and Alberta Health Services, Calgary, Canada

COVID-19 Infection Prevention and Control Isolation Precautions with a Focus on Immunocompromised Patients in Calgary, Canada

Territorial Acknowledgement

I acknowledge the traditional territories of the Blackfoot and Treaty 7 peoples including the Siksika, Piikuni, Kainai, Tsuut’ina, and Stoney Nakoda First Nations. Calgary is also hometo the Metis Nation of Alberta, Region III.

Faculty/Presenter Disclosures• Financial disclosure affiliations

• Honoraria: None• Speakers' Bureaux, advisory boards: Received funding to attend a meeting

on HAI from the CDC and bioMerieux• Grants/Clinical Trials: Local PI for the STRIVE S. aureus vaccine trial spinal

surgery (Pfizer) and holds grants from CIHR, AI-HS, PHAC, AH, AHS, EDT. • Patents, royalties: None• Investments in health organizations: None• Other affiliations: Member of committees with PHAC, CIHR, Cochrane

Collaboration Resp Virus Working Group, WHO AGISAR, WHO Infection Prevention and Control Research and Development Expert Group for COVID-19, WHO Health Emergencies Programme, AHS Scientific Advisory Group

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Outline and Objectives

• Presence of viable SARS-CoV-2 in body fluids

• Assess studies of SARS-CoV-2 cultivatability in patients with COVID including immuno-compromised patients

• Review the implications for Isolation Precautions

Viable SARS-CoV-2 Detection• BAL samples/ETT secretions /sputum (Zhu NEJM, van Kampen )• Nasopharyngeal swabs/oropharyngeal swabs /saliva (NP/OP) swabs

studies demonstrate viable virus gone by Day 7-8 in immunocompetentpersons but up to 15+ days in immunocompromised/severely ill/elderly

viable virus does not necessarily correlate with RT-PCR positivity; f (timing,technique, platform used )

Serum/blood None to date (only + RT-PCR in serum in patients)

• Stool/Urine At least 6 studies now found cultivatable virus in stool and 2 in urine and

transmission to ferrets demonstrated with inoculation by these + specimens• Placenta + immunohistochemistry( N protein ) in placental tissues

Wolfel et al Nature. 2020 Apr 1. doi: 10.1038/s41586-020-2196-x.; Bullard J et al Clin infect Dis.https://doi.org/10.1093/cid/ciaa638Xiao F et al. Sun Infectious SARS-CoV-2 in Feces…. Emerg Infect Dis. 2020;26(8); Wang Wet al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. 2020;323(18):1843-1844. La Scola B.et al. Viral RNA load as determined by cell culture …Eur J Clin Microbiol Infect Dis 39, 1059–1061 (2020); van Kampen J et al Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID19): duration and key determinant. 2020.https://doi.org/10.1101/2020.06.08.20125310doi

Wolfel et al Nature. 2020 Apr 1. doi: 10.1038/s41586-020-2196-x.

Virus wasreadily isolated during the first week of symptoms from a considerablefraction of samples (16.66% in swabs, 83.33% in sputum samples)

Population: Healthy young males n=10

No isolates of virus obtained from samples taken after day 8 in spite of ongoing high viral copies by RT-PCR

Viral Cultivatability

Bullard J et al . Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis. 2020 May 22:ciaa638. doi: 10.1093/cid/ciaa638. Epub ahead of print.

Figure 1: SARS-CoV-2 viral dynamics as expressed by E gene RT-PCR Ct value and cell culture TCID50/mL, over time (days).

Figure 3: Comparison of symptom onset to test (days) to the probability of successful cultivation on Vero cells and SARS-CoV-2 E gene RT-PCR Ct (Ct) value.

Population: Adults ( 90 samples) ? # patients ; 26 +s NP and ETT specimens so presume ICU pts

Ct values > 24 & syx > 8 days may be used to predict non viable virus

Viral Cultivatability

Van Kampen et al . 2020. Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants. medRxiv preprint doi: https://doi.org/10.1101/2020.06.08.20125310

Population: Adults (129 hospitalized /89 ICU/11 severe ICH [AlloSCT; HIV < 200CD4; active chemo; SOT < 6 mos; biologics/pred> 30 mg] ) 23/33 + pts/samples

Only 4/33 samples + severe of 20 ICH samples Probability of + viral culture <5% at > 15.2 days post syx

onset (95% CI of 13.4 – 17.2) Consider severity illness as part of duration shedding

viable virus

Van Kampen et al . 2020.

Van Kampen et al . Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants. medRxiv preprint doi: https://doi.org/10.1101/2020.06.08.20125310.this version posted June 9, 2020.

Jaafar R et al . Correlation between 3790 qPCR positives samples and positive cell cultures including 1941 SARS-CoV-2 isolates. Clin Infect Dis 2020 Sep 28;ciaa1491. doi: 10.1093/cid/ciaa1491. Online ahead of print

Population: Not specified Used subculture to find

cultivatable virus at higher Ct values based on their platform

Reported < 3% + at Ct value 35 and 20% + Ct 30

Very few + cultures by week 3

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6-Sep 11-Sep 16-Sep 21-Sep 26-Sep 1-Oct 6-Oct 11-Oct

Post

rem

Viral Load

NP log10 (pfu/ml) Saliva log10 (pfu/ml)

Viral Cultivatability Early Cardiac Transplantation

Cardiac transplant patient # 1 • Neg COVID on Sept 2 but + Sept 5• R+/I+ virus Log 3-4 pfu/ml present Sept

8 - Oct 1 saliva and NP • Rendered negative with remdesivir

between Oct 1-8 • Total 26 -33 days + virus culture

Cardiac transplant #2 • COVID + Sept 23 and found log 3 and

log 2 pfu/ml to Oct 15 and ↓ to – NP and 7x101 pfu/ml sputum post remdesivir Oct 18

• Total 26+ days + virus culture Unpublished Data: U of Alberta and U of Calgary and ProvLab AB – D Evans, J Lin , T Louie, L Ward, L Kiplagat, R Mallot, B Berenger, J Conly,

Quantitative SARS-CoV-2 Detection in Dried Spittle

Unpublished Data: U of Alberta and U of Calgary and ProvLab AB – D Evans, J Lin , J Conly, T Louie, L Ward, L Kiplagat, R Mallot, B Berenger

Sample Location

Sample Arm A (dessicated)Sample Arm B (with

DMEM)

Titer (PFU/mL) Titer (PFU/mL)

Baseline 2.30x103 1.00x103

Ledge 2.05x103, 1.50x103 1.25x103

Ledge 8.50x 102 9.00x102

Bathroom 1.45x104 8.00x102TCID50 x 0.7 = pfu/ml

• Spittle samples of ~ 1 ml on petri dishes from• known + patient • Control with DMEM vs samples allowed to

dessicate over 2-2.5 hours

Fontana, L., Villamagna, A., Sikka, M., & McGregor, J. (2020). Understanding Viral Shedding of SARS-CoV-2: Review of Current Literature. Infection Control & Hospital Epidemiology, 1-35. doi:10.1017/ice.2020.127

Summary Key Clinico-epidemiologic Findings • Concentrations of SARS-CoV-2 RNA measured in UR specimens decline after

onset of symptoms and recovered patients can continue to have SARS-CoV-2 RNA detected in their UR specimens for up to 12 weeks

• The likelihood of recovering replication-competent virus declines after onset of symptoms. With mild to moderate COVID-19, replication-competent virus has not been recovered after 10 days following symptom onset

• Recovery of replication-competent virus between 10 and 20 days after symptom onset found in some persons with severe COVID-19 complicated by immunocompromised state (van Kampen et al., 2020) but 95% negative for replication-competent virus 15 days post symptom onset

• A large contact tracing study demonstrated that high-risk household and hospital contacts did not develop infection if their exposure to a case patient started 6 days or more after the case patient’s illness onset

Reference : Duration of Isolation and Precautions for Adults with COVID-19 CDC Oct 19 2020 https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

Images; AHS Donning and Doffing

Spectrum “APP” as a Digital IPC Tool

• Spectrum COVID-19 “app”• iOS and Android compatible • Focused on IPC issues• Completely customizable • Acts as a personal digital assistant • Contains still photos and live

video links for donning/doffing• Recommendations for isolation based

on local guidelines