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

Transcription

1 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

2 None Disclosures

3 Introduction As of 9/ 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.

4 SARS H1N1 H5N1 H1N1pdm09 JID 2014

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6 Anti-MERS-COV Convalescent plasma Therapy (MERS Study) ClinicalTrials.gov NCT

7 Testing Enzyme Linked Immunosorbent Assay (ELISA) Indirect Fluorescent Antibody (IFA) technique of serum IgG MERS-CoV antibodies

8 Number of subjects who were tested N= 443 Healthcare Workers with history of MERS-CoV exposure N=230 Patients with suspected or confirmed MERS-CoV N=196 Household contact with MERS-CoV patients N=17 Positive RT-PCR N=11(4.7%) Negative RT-PCR N=219(95.3%) Positive RT-PCR N= 5(2.6%) Negative RT-PCR N= 191(97.4%) Positive RT-PCR Negative RT- PCR N=17(100%) Reactive ELISA Reactive ELISA Reactive ELISA Reactive ELISA Reactive ELISA Reactive ELISA N=4(36.4%) N= 2(40%) N=6(3%)

9 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 /10 1/ F ARI /10 negative 3 40 F ARI /10 1: M ARI /10 1: M ARI /10 1: M ARI <1/10 negative 7 69 M ARI /1000 1: M ARI <1/10 negative 9 46 F HCW /10 1: F HCW /10 1: M HCW /10 1: F HCW /10 1:10

10 Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 Month 8 Month 9 Month 10 Optic Density Ratio for ELISA RT-PCR ICU WARD HOME Vasopressors Mechanical Ventilation Dialysis IFA 1:1280 1:160 IFA= NEGATIVE 1.5 1:1280 1: :1280 1:160 1:160 0

11 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.

12 Future Directions Neutralization assay (NIAID) Different process for screening blood donors Monoclonal and polycolonal antibodies Other therapies: Lopinavir/ritonavir combined with interferon (MIRACLE trial)

13 Thank You

14 Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 Month 8 Month 9 Month 10 Optic Density Ratio for ELISA Convalescent Plasma Therapy for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Feasibility Study in the Kingdom of Saudi Arabia Yaseen.M.Arabi 1, A. Hajeer 1, H. Balkhy 1, S. Johani 1, A. Aldawood 1, S. AlQahtani 1, A. Omari 2, F. Hameed 3, F. Hayden 4, T. Luke 5, R. Fowler 6 A. Bouchamma 1, N. Shindo 7 K. Khairy 1, G. Carson 8 ; Y. Taha 9 ; M.Sadat 1 ; M. Alahmadi 1, 1 King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia, 2 Security Forces Hospital, Riyadh, Saudi Arabia, 3 King Abdulaziz Medical City, Jeddah, 4 Saudi, University of Virginia School of Medicine, USA, 5 Viral & Rickettsial Diseases Department, USA, 6 Sunnybrook Health Sciences Centre, Canada, 7 World Health Organization, Switzerland, 8 University of Oxford Centre for Tropical Medicine, UK, 9 King Abdulaziz Medical City Al-Ahsa, Saudi Arabia. Rationale 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 Methods 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. Table 1. Characteristics of subjects who were screened as potential donors for convalescent plasma in the Middle East Respiratory Syndrome (MERS-CoV) infection 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 Results Table 2: Characteristics of subjects with ELISA-reactive and IFA-reactive tests to the Middle East Respiratory Syndrome Coronavirus (MERS- CoV). ). Subject Age Gender Presenting MERS-PCR O.D. Ratio IFA symptoms 1 70 M ARI / F ARI negative 3 40 F ARI : M ARI : M ARI : M ARI 1.62 negative 7 69 M ARI : M ARI 1.86 negative 9 46 F HCW : F HCW : M HCW : F HCW :10 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. Figure 1 Number of subjects who were tested N= 443 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. RT-PCR ICU WARD HOME Conclusions In our cohorts anti-mers-cov antibody titers were uncommonly detected, and generally low. Vasopressors Healthcare workers with history of MERS-CoV exposure N=230 Patients with suspected or confirmed MERS-CoV N=196 Household contact of MERS-CoV patients N= Mechanical Ventilation Dialysis 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 Positive RT-PCR N=11(4.7%) Negative RT- PCR N=219(95.3%) Positive RT-PCR N= 5(2.6%) Negative RT- PCR N= 191(97.4%) Positive RT-PCR Negative RT- PCR N=17(100%) IFA 1:1280 1:160 IFA= NEGATIVE 1.5 1:1280 1:160 Reactive ELISA N=4(36.4%) Reactive ELISA Reactive ELISA N= 2(40%) Reactive ELISA N=6(3%) Reactive ELISA Reactive ELISA :1280 1:160 1:160 Source of funding: King Abdullah International Medical Research Center Study registration: Clinicaltrials.gov (NCT ). arabi@ngha.med.sa