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

O'Donnell, Max R; Grinsztejn, Beatriz; Cummings, Matthew J; Justman, Jessica E; Lamb, Matthew R; Eckhardt, Christina M; Philip, Neena M; Cheung, Ying Kuen; Gupta, Vinay; João, Esau; Pilotto, Jose H; Diniz, Maria Pia; Cardoso, Sandra Wagner; Abrams, Darryl; Rajagopalan, Kartik N; Borden, Sarah E; Wolf, Allison; Sidi, Leon Claude; Vizzoni, Alexandre; Veloso, Valdilea G; Bitan, Zachary C; Scotto, Dawn E; Meyer, Benjamin J; Jacobson, Samuel D; Kantor, Alex; Mishra, Nischay; Chauhan, Lokendra V; Stone, Elizabeth F; Dei Zotti, Flavia; La Carpia, Francesca; Hudson, Krystalyn E; Ferrara, Stephen A; Schwartz, Joseph; Stotler, Brie A; Lin, Wen-Hsuan W; Wontakal, Sandeep N; Shaz, Beth; Briese, Thomas; Hod, Eldad A; Spitalnik, Steven L; Eisenberger, Andrew; Lipkin, Walter I

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. METHODS We conducted a randomized, double-blind, placebo-controlled trial among adults hospitalized with severe and critical COVID-19 at five sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized in a 2:1 ratio to receive a single transfusion of either convalescent plasma or placebo (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. 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 (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. CONCLUSIONS In adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in clinical status at day 28. However, a significant improvement in mortality was observed, which warrants further evaluation. TRIAL REGISTRATION ClinicalTrials.gov, NCT04359810FUNDING. Amazon Foundation. Skoll Foundation.