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Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: A Feasibility Study Yaseen Arabi, MD, FCCP, FCCM Chairman, Intensive Care Department Medical Director, Respiratory Services Professor , College of Medicine King Saud Bin Abdulaziz University for Health Sciences Riyadh, Kingdom of Saudi Arabia

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Page 1: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Convalescent Plasma Therapy for

Middle East Respiratory Syndrome

Coronavirus (MERS-CoV) Infection:

A Feasibility Study Yaseen Arabi, MD, FCCP, FCCMChairman, Intensive Care Department

Medical Director, Respiratory Services

Professor, College of Medicine

King Saud Bin Abdulaziz University for Health Sciences

Riyadh, Kingdom of Saudi Arabia

Page 2: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Disclosures

• None

Page 3: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Introduction

• As of 9/2015

• 1595 laboratory-confirmed MERS-CoV infection

from 26 countries

• 571 (35.7%) deaths.

• >85% of cases have been in Saudi Arabia.

• There is no specific treatment of proven

effectiveness for MERS-CoV infection.

Page 4: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

JID 2014

• SARS

• H1N1

• H5N1

• H1N1pdm09

Page 5: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,
Page 6: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Anti-MERS-COV Convalescent plasma

Therapy (MERS Study)

ClinicalTrials.gov

NCT02190799

Page 7: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Testing

• Enzyme Linked Immunosorbent Assay

(ELISA)

• Indirect Fluorescent Antibody (IFA)

technique of serum IgG MERS-CoV

antibodies

Page 8: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Number of

subjects

who were tested

N= 443

Positive

RT-PCR

N=11(4.7%)

Patients with suspected or confirmed

MERS-CoV

N=196

Healthcare Workers with history of

MERS-CoV exposure

N=230

Household contact with

MERS-CoV patients

N=17

Negative

RT-PCR N=219(95.3%)

Reactive ELISA

N=4(36.4%)

Reactive ELISA

N=0(0%)

Positive

RT-PCR

N= 5(2.6%)

Negative

RT-PCR

N= 191(97.4%)

Reactive ELISA

N= 2(40%)

Reactive ELISA

N=6(3%)

Positive

RT-PCR

N=0(0%)

Negative RT-

PCR

N=17(100%)

Reactive ELISA

N=0(0%)

Reactive ELISA

N=0(0%)

Page 9: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Subjects with ELISA-reactive

and IFA-reactive tests

Subject Age Gender Presenting

symptoms

MERS-PCR Time from

infection/exposure

and sample

collection (days)

O.D. Ratio IFA New IFA

1 70 M ARI – 35 2.00 1/10 1/10

2 61 F ARI + 10 1.12 1/10 negative

3 40 F ARI – 4 3.66 1/10 1:20

4 63 M ARI – 27 3.95 1/10 1:80

5 76 M ARI + 13 2.59 1/10 1:20

6 73 M ARI – 4 1.62 <1/10 negative

7 69 M ARI + 87 4.70 1/1000 1:1280

8 71 M ARI – 9 1.86 <1/10 negative

9 46 F HCW + 24 5.51 1/10 1:40

10 27 F HCW + 273 2.33 1/10 1:20

11 31 M HCW + 365 1.46 1/10 1:10

12 33 F HCW + 365 2.34 1/10 1:10

Page 10: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

0

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ICU WARD HOME

Vasopressors

Mechanical Ventilation

Dialysis

RT-PCR

Op

tic D

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sit

y R

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o f

or

EL

ISA

1:1280

1:1280

1:1280

IFA

1:160

1:160

1:160

1:160 IFA= NEGATIVE

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nth

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Page 11: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Conclusions

• No subject met both clinical and laboratory

criteria for plasma donation.

• Evaluating convalescent plasma for the

treatment of MERS-CoV in a clinical trial may

challenging due to a small pool of potential

donors with sufficient antibody titers.

Page 12: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Future Directions

• Neutralization assay (NIAID)

• Different process for screening blood donors

• Monoclonal and polycolonal antibodies

• Other therapies: Lopinavir/ritonavir combined

with interferon (MIRACLE trial)

Page 13: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Thank You

Page 14: Convalescent Plasma Therapy for Middle East Respiratory ...€¦ · Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection ... Al-Ahsa ,

Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Feasibility Study in the Kingdom

of Saudi Arabia

Yaseen.M.Arabi1, A. Hajeer1, H. Balkhy1, S. Johani1, A. Aldawood1, S. AlQahtani1, A. Omari2, F. Hameed3, F. Hayden4, T. Luke5, R. Fowler6

A. Bouchamma1, N. Shindo7 K. Khairy1, G. Carson8; Y. Taha9; M.Sadat1; M. Alahmadi1,

1King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia, 2Security Forces

Hospital, Riyadh, Saudi Arabia, 3King Abdulaziz Medical City, Jeddah, 4Saudi, University of Virginia School of Medicine, USA, 5Viral & Rickettsial Diseases Department

, USA, 6Sunnybrook Health Sciences Centre, Canada, 7World Health Organization, Switzerland, 8University of Oxford Centre for Tropical Medicine, UK, 9King Abdulaziz Medical City

Al-Ahsa , Saudi Arabia.

Methods

Rationale Results

Conclusions

Source of funding: King Abdullah International Medical Research Center

Study registration: Clinicaltrials.gov (NCT02190799).

Email: [email protected]

• Between September 2012 and September 2015, 1595 laboratory-confirmed human

cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from

23 countries, including at least 571 (35.7%) deaths, have been reported.

• >85% of cases have been in Saudi Arabia.

• There is not yet specific treatment of proven effectiveness for MERS-CoV infection.

• The objective of this study is to explore the feasibility of collecting convalescent

plasma for possible therapy of the Middle East Respiratory Syndrome coronavirus

(MERS-CoV) infection

• The study protocol was developed in collaboration with King Abdullah International

Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection

Control Center and the World Health Organization - International Severe Acute

Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV

Working Group

• We screened potential donors (n = 443) from 3 cohorts exposed healthcare workers

(HCWs), MERS-CoV patients and household contacts) using Enzyme Linked

Immunosorbent Assay (ELISA) and Indirect Fluorescent Antibody (IFA) technique of

serum IgG MERS-CoV antibodies.

Figure 1

Table 1. Characteristics of subjects who were screened as potential donors for convalescent plasma in the

Middle East Respiratory Syndrome (MERS-CoV) infection

Number of subjects

who were tested

N= 443

Positive RT-PCR

N=11(4.7%)

Patients with suspected or confirmed MERS-CoV

N=196

Healthcare workers with history of MERS-CoV

exposure

N=230

Household contact of

MERS-CoV patients

N=17

Negative RT-PCR

N=219(95.3%)

Reactive ELISA

N=4(36.4%)

Reactive ELISA

N=0(0%)

Positive RT-PCR N= 5(2.6%)

Negative RT-PCR N=

191(97.4%)

Reactive ELISA

N= 2(40%)

Reactive ELISA

N=6(3%)

Positive RT-PCR N=0(0%)

Negative RT-

PCR

N=17(100%)

Reactive ELISA

N=0(0%)

Reactive ELISA

N=0(0%)

Healthcare workers exposed to laboratory-confirmed MERS-CoV patients N= 230

Age, median (Q1, Q3) years 35(29, 42)

Male gender, n (%) 34(14.7)

Type of exposure, n (%)

Intubation 52(22.6)

Bronchoscopy 22(9.6)

Tracheal Suctioning or inhalation therapy 72(31.3)

Patient care 117(50.9)

Reported total duration of exposure*, n (%)

≤24 hours 66/199(33.2)

>24 hours 133/199(66.8)

Reported exposure intensity$, n (%)

Mild 108/200(54)

Moderate 60/200(30)

Severe 31/200(15.5)

Laboratory confirmed MERS-CoV infection, n (%) 11(4.8)

Positive ELISA, n (%) 4(1.7)

Median time to testing positive (Q1, Q3), days 381(246, 485)

Patients with suspected or laboratory-confirmed MERS-CoV N =196

Age, median (Q1, Q3), years 65 (49,76)

Male gender, n (%) 97(49.5)

Disposition, n (%)

ICU 11(5.8)

ER 183(88.8)

Ward 2(0.97)

Laboratory confirmed MERS-CoV infection, n (%) 5(2.6)

Positive ELISA, n (%) 8(4.1)

Median time to testing positive (Q1, Q3), days 7(4,12)

Household contacts to confirmed MERS-CoV patients N= 17

Age, median (range), years 37(26, 46)

Male gender, n (%) 6(35.3)

Laboratory confirmed MERS-CoV infection, n (%) 0(0%)

Positive ELISA, n (%) 0(0%)

Median time to antibody testing (Q1, Q3)), days 34(34, 34)

ELISA: Enzyme-linked immunosorbent assay; HCW: healthcare worker; ICU: intensive care unit; ER: Emergency Room

* This question was answered on a self-administered survey. Only 199 HCWs answered this question.

$ This question was answered on a self-administered survey. Only 200 HCWs answered this question

Table 2: Characteristics of subjects with ELISA-reactive and IFA-reactive tests to the Middle East Respiratory Syndrome Coronavirus (MERS-

CoV). ).

O.D. ratio= O.D. value of patient sample/O.D. value of calibrator. O.D.- optic density, IFA: Immunofluorescent Assay, ARI: acute respiratory illness.

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Vasopressors

Mechanical Ventilation

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Optic D

ensity R

atio for

ELIS

A

1:1280

1:1280

1:1280

IFA

1:160

1:160

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1:160IFA= NEGATIVE

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Figure 2. The clinical and laboratory timeline of the only patient who had high IFA (Indirect Fluorescent-

Antibody) of 1/1280. The high titer occurred while the patient had active MERS-CoV infection and was

critically ill. High titers started declining as he recovered from critical illness.

• In our cohorts anti-MERS-CoV antibody titers were uncommonly detected, and generally low.

• Evaluating convalescent plasma for the treatment of MERS-CoV in a clinical trial may be challenging due to

a small pool of potential donors with sufficient antibody titers.

Subject Age Gender Presenting

symptoms

MERS-PCR O.D. Ratio IFA

1 70 M ARI – 2.00 1/10

2 61 F ARI + 1.12 negative

3 40 F ARI – 3.66 1:20

4 63 M ARI – 3.95 1:80

5 76 M ARI + 2.59 1:20

6 73 M ARI – 1.62 negative

7 69 M ARI + 4.70 1:1280

8 71 M ARI – 1.86 negative

9 46 F HCW + 5.51 1:40

10 27 F HCW + 2.33 1:20

11 31 M HCW + 1.46 1:10

12 33 F HCW + 2.34 1:10