title: Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol.
abstract: As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).
authors.affiliation: Intensive Care Department, Respiratory Services, College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, P.O. Box 22490, Riyadh, 11426 Saudi Arabia.
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Arabi
authors.affiliation: Infection Control Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Hanan
authors.initials: H
authors.lastname: Balkhy
authors.affiliation: Pathology and Laboratory Department, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Hajeer
authors.affiliation: Intensive Care Department, Respiratory Services, College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, P.O. Box 22490, Riyadh, 11426 Saudi Arabia.
authors.forename: Abderrezak
authors.initials: A
authors.lastname: Bouchama
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA USA.
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hayden
authors.affiliation: Critical Care and Infection Control Department, Security Forces Hospital, AlFaisal University, Riyadh, Saudi Arabia.
authors.forename: Awad
authors.initials: A
authors.lastname: Al-Omari
authors.affiliation: Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia.
authors.forename: Fahad M
authors.initials: FM
authors.lastname: Al-Hameed
authors.affiliation: Infectious Diseases, Department of Medicine, King Abdulaziz Medical City, Al-Ahsa, Saudi Arabia.
authors.forename: Yusri
authors.initials: Y
authors.lastname: Taha
authors.affiliation: Pandemic and Epidemic Diseases Department, World Health Organization, Geneva, Switzerland.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Shindo
authors.affiliation: Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.
authors.forename: John
authors.initials: J
authors.lastname: Whitehead
authors.affiliation: Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Laura
authors.initials: L
authors.lastname: Merson
authors.affiliation: Pathology and Laboratory Department, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Sameera
authors.initials: S
authors.lastname: AlJohani
authors.affiliation: Pathology and Laboratory Department, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Khairy
authors.affiliation: University of Oxford Centre for Tropical Medicine (CCVTM), Churchill Hospital Old Road, Headington, Oxford, OX3 7LE UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Carson
authors.affiliation: Viral and Rickettsial Diseases Department, Naval Medical Research Center, The Henry Jackson Foundation, 6720A Rockledge Drive #100, Bethesda, MD 20817 USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Luke
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, Frederick, MD USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hensley
authors.affiliation: Intensive Care Department, Respiratory Services, College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, P.O. Box 22490, Riyadh, 11426 Saudi Arabia.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Al-Dawood
authors.affiliation: Intensive Care Department, Respiratory Services, College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, P.O. Box 22490, Riyadh, 11426 Saudi Arabia.
authors.forename: Saad
authors.initials: S
authors.lastname: Al-Qahtani
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910 USA.
authors.forename: Kayvon
authors.initials: K
authors.lastname: Modjarrad
authors.affiliation: Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Musharaf
authors.initials: M
authors.lastname: Sadat
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Center, P. Debyelaan 25, 6202AZ Maastricht, The Netherlands.
authors.forename: Gernot
authors.initials: G
authors.lastname: Rohde
authors.affiliation: The French Infectious Disease Society, Universite Paris Diderot, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Leport
authors.affiliation: Department of Medicine and Institute of Health Policy Management and Evaluation, AMR Infection Control and Publications AIP/PED/HSE/HQ, University of Toronto, Toronto, Canada ; Department of Critical Care Medicine and Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Fowler
keywords: Convalescent plasma; Genome; Intensive care; MERS-CoV; Middle east respiratory syndrome coronavirus; Neutralizing antibodies; Serology; Viral pneumonia