1
Title: A randomized, double-blind, controlled trial of convalescent plasma in adults with severe
COVID-19
Authors:
Max R. O’Donnell,
1,2,3
Beatriz Grinsztejn,
4
Matthew J. Cummings,
1,3
Jessica Justman,
5,6
Matthew R. Lamb,
2,5
Christina M. Eckhardt,
1
Neena M. Philip,
5
Ying Kuen Cheung,
7
Vinay
Gupta,
8
Esau João,
9
Jose Henrique Pilotto,
10
Maria Pia Diniz,
4
Sandra Wagner Cardoso,
4
Darryl
Abrams,
1
Kartik Rajagopalan,
1
Sarah Borden,
1
Allison Wolf,
1
Leon Claude Sidi,
9
Alexandre
Vizzoni,
4
Valdilea G. Veloso,
4
Zachary C. Bitan,
11
Dawn E. Scotto,
1
Benjamin J. Meyer,
12
Samuel D. Jacobson,
12
Alex Kantor,
1
Nischay Mishra,
2,3
Lokendra V. Chauhan,
3
Elizabeth
Stone,
11
Flavia Dei Zotti,
11
Francesca La Carpia,
11
Krystalyn E. Hudson,
11
Stephen A. Ferrera,
11
Joseph Schwartz,
11
Brie Stotler,
11
Wen-Hsuan Lin,
11
Sandeep Wontakal,
11
Beth Shaz,
13
Thomas
Briese,
2,3
Eldad A. Hod,
11
Steven L. Spitalnik,
11
Andrew Eisenberger,
14
W. Ian Lipkin
2,3,11
Affiliations:
1
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia
University Irving Medical Center, New York, NY, USA; 622 West 168
th
Street, New York, NY,
10032, USA.
2
Department of Epidemiology, Columbia University Mailman School of Public Health, New York,
NY, USA; 722 West 168
th
Street, New York, NY, 10032, USA.
3
Center for Infection and Immunity, Columbia University Mailman School of Public Health, New
York, NY, USA; 722 West 168
th
Street, New York, NY, 10032, USA.
4
Instituto Nacional de Infectologia Evandro Chagas, Av. Brasil, 4365 - Manguinhos, Rio de
Janeiro , 21040-360, Brazil
5
ICAP, Columbia University Mailman School of Public Health, New York, NY, USA; 722 West
168
th
Street, New York, NY, 10032, USA.
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253373doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
2
6
Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical
Center, New York, NY, USA; 622 West 168
th
Street, New York, NY, 10032, USA.
7
Department of Biostatistics, Columbia University Mailman School of Public Health, New York,
NY, USA; 722 West 168
th
Street, New York, NY, 10032, USA.
8
Institute for Health Metrics and Evaluation, University of Washington, Box 351615, 3980 15th
Ave NE, Seattle, WA, 98195, USA
9
Hospital Federal dos Servidores do Estado, R. Sacadura Cabral, 178 - Saúde, Rio de Janeiro,
20221-161, Brazil
10
Hospital Geral de Nova Iguaçu, Av. Henrique Duque Estrada Meyer, 953 - Posse, Nova
Iguaçu and Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz – Fiocruz, Rio
de Janeiro, 21040-360, Brazil
11
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 622
West 168
th
Street, New York, NY, 10032, USA.
12
Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; 630 West
168
th
Street, New York, NY, 10032, USA.
13
New York Blood Center, 310 E 67th Street, New York, NY 10065, New York, NY, USA.
14
Division of Hematology and Oncology, Department of Medicine, Columbia University Irving
Medical Center, 622 West 168
th
Street, New York, NY, 10032, USA.
Corresponding Author: Max R. O’Donnell, MD, MPH, Division of Pulmonary, Allergy, and
Critical Care Medicine, Columbia University Irving Medical Center, 622 West 168
th
St, PH 8E-
101, New York, NY, 10032, USA. Email: mo2130@columbia.edu; Telephone: +12123055794;
Fax: +12123058464
Abstract Word Count: 335
Manuscript total word count: 3,499
Running title: Trial of convalescent plasma in severe COVID-19
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253373doi: medRxiv preprint
3
Web Supplement: This article has an online supplement.
Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04359810
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253373doi: medRxiv preprint
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Abstract
Background: Although convalescent plasma has been widely used to treat severe coronavirus
disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are
limited.
Objective: To evaluate the clinical efficacy and safety of convalescent plasma among adults
hospitalized with severe and critical COVID-19.
Design: Randomized, double-blind, controlled, multicenter, phase 2 trial conducted from April
21
st
to November 27
th
, 2020.
Setting: Five hospitals in New York City (NY, USA) and Rio de Janeiro (Brazil).
Participants: Hospitalized patients aged
≥
18 years with laboratory-confirmed COVID-19,
infiltrates on chest imaging and oxygen saturation
≤
94% on room air or requirement for
supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane
oxygenation.
Intervention: Participants were randomized 2:1 to a single transfusion of either 1 unit of
convalescent or normal control plasma.
Measurements: The primary outcome was clinical status at 28 days, measured using an ordinal
scale and analyzed using a proportional odds model in the intention-to-treat population.
Results: Of 223 participants enrolled, 150 were randomized to receive convalescent plasma
and 73 to normal control plasma. At 28 days, no significant improvement in clinical status was
observed in participants randomized to convalescent plasma (with an odds ratio (OR) of a 1-
point improvement in the scale: 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180).
However, 28-day mortality was significantly lower in participants randomized to convalescent
plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-
0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused
convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab
samples (n=40) from Brazil that underwent genomic sequencing, no evidence of neutralization-
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253373doi: medRxiv preprint
5
escape mutants was detected. Serious adverse events occurred in 39/147 (27%) participants
who received convalescent plasma and 26/72 (36%) participants who received control plasma.
Limitations: Some participants did not receive high-titer convalescent plasma.
Conclusion: In adults hospitalized with severe COVID-19, use of convalescent plasma was not
associated with significant improvement in 28 days clinical status. The significant reduction in
mortality associated with convalescent plasma, however, may warrant further evaluation.
Registration: ClinicalTrials.gov, NCT04359810
Funding: Amazon Foundation
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253373doi: medRxiv preprint
