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
Disclosures
• None
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.
JID 2014
• SARS
• H1N1
• H5N1
• H1N1pdm09
Anti-MERS-COV Convalescent plasma
Therapy (MERS Study)
ClinicalTrials.gov
NCT02190799
Testing
• Enzyme Linked Immunosorbent Assay
(ELISA)
• Indirect Fluorescent Antibody (IFA)
technique of serum IgG MERS-CoV
antibodies
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%)
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
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
ICU WARD HOME
Vasopressors
Mechanical Ventilation
Dialysis
RT-PCR
Op
tic D
en
sit
y R
ati
o f
or
EL
ISA
1:1280
1:1280
1:1280
IFA
1:160
1:160
1:160
1:160 IFA= NEGATIVE
Mo
nth
1
Mo
nth
2
Mo
nth
3
Mo
nth
4
Mo
nth
5
Mo
nth
6
Mo
nth
7
Mo
nth
8
Mo
nth
9
Mo
nth
10
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.
Future Directions
• Neutralization assay (NIAID)
• Different process for screening blood donors
• Monoclonal and polycolonal antibodies
• Other therapies: Lopinavir/ritonavir combined
with interferon (MIRACLE trial)
Thank You
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.
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
ICU WARD HOME
Vasopressors
Mechanical Ventilation
Dialysis
RT-PCR
Optic D
ensity R
atio for
ELIS
A
1:1280
1:1280
1:1280
IFA
1:160
1:160
1:160
1:160IFA= NEGATIVE
Mo
nth
1
Mo
nth
2
Mo
nth
3
Mo
nth
4
Mo
nth
5
Mo
nth
6
Mo
nth
7
Mo
nth
8
Mo
nth
9
Mo
nth
10
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
