A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19

doi:10.1172/JCI150646

Clinical Trial

. 2021 Jul 1;131(13):e150646.

doi: 10.1172/JCI150646.

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19

Max R O'Donnell^{1

2

3}, Beatriz Grinsztejn⁴, Matthew J Cummings^{1

3}, Jessica E Justman^{2

5

6}, Matthew R Lamb^{2

5}, Christina M Eckhardt¹, Neena M Philip⁵, Ying Kuen Cheung⁷, Vinay Gupta⁸, Esau João⁹, Jose Henrique Pilotto¹⁰, Maria Pia Diniz⁴, Sandra Wagner Cardoso⁴, Darryl Abrams¹, Kartik N Rajagopalan¹, Sarah E Borden¹, Allison Wolf¹, Leon Claude Sidi⁹, Alexandre Vizzoni⁴, Valdilea G Veloso⁴, Zachary C Bitan¹¹, Dawn E Scotto¹, Benjamin J Meyer¹², Samuel D Jacobson¹², Alex Kantor¹, Nischay Mishra³, Lokendra V Chauhan³, Elizabeth F Stone¹¹, Flavia Dei Zotti¹¹, Francesca La Carpia¹¹, Krystalyn E Hudson¹¹, Stephen A Ferrara¹¹, Joseph Schwartz¹¹, Brie A Stotler¹¹, Wen-Hsuan W Lin¹¹, Sandeep N Wontakal¹¹, Beth Shaz¹³, Thomas Briese³, Eldad A Hod¹¹, Steven L Spitalnik¹¹, Andrew Eisenberger¹⁴, Walter I Lipkin^{2

3

11}

Affiliations

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
² Department of Epidemiology, and.
³ Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, New York, USA.
⁴ Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil.
⁵ ICAP, Columbia University Mailman School of Public Health, New York, New York, USA.
⁶ Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
⁷ Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York, USA.
⁸ Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA.
⁹ Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil.
¹⁰ Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil and Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.
¹¹ Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
¹² Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
¹³ New York Blood Center, New York, New York, USA.
¹⁴ Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

PMID: 33974559
PMCID: PMC8245169
DOI: 10.1172/JCI150646

Free PMC article

Clinical Trial

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19

Max R O'Donnell et al. J Clin Invest. 2021.

Free PMC article

. 2021 Jul 1;131(13):e150646.

doi: 10.1172/JCI150646.

Authors

Affiliations

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
² Department of Epidemiology, and.
³ Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, New York, USA.
⁴ Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil.
⁵ ICAP, Columbia University Mailman School of Public Health, New York, New York, USA.
⁶ Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
⁷ Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York, USA.
⁸ Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA.
⁹ Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil.
¹⁰ Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil and Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.
¹¹ Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
¹² Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
¹³ New York Blood Center, New York, New York, USA.
¹⁴ Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

PMID: 33974559
PMCID: PMC8245169
DOI: 10.1172/JCI150646

Abstract

BACKGROUNDAlthough 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.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 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 from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.

Keywords: COVID-19; Hypoxia.

Conflict of interest statement

Conflict of interest: MRO and MJC participated as investigators for clinical trials evaluating the efficacy and safety of remdesivir in hospitalized patients with COVID-19, sponsored by Gilead Sciences. VG is employed by Amazon Care.

Figures

**Figure 2. Kaplan-Meier estimates of mortality, stratified by treatment group.**

**Figure 3. Time-to-clinical improvement with death considered a competing risk, stratified by treatment group.**

**Figure 4. Subgroup analyses of primary outcome of clinical status at 28 days, adjusted for age and sex.**
pOR, proportional odds ratio.

See this image and copyright information in PMC

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