Neutralizing Covid-19 Convalescent Plasma In Adults Hospitalized With Covid-19: A Blinded, Randomized, Placebo-controlled Trial
Background: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. Research Question: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? Study Design and Methods: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies (“serostatus”) at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. Results: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR, 1.04; one-seventh support interval [1/7 SI], 0.82-1.33), in patients without endogenous antibodies (aOR, 1.15; 1/7 SI, 0.74-1.80), or in patients with endogenous antibodies (aOR, 0.96; 1/7 SI, 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89 of 482 (18.5%) patients in the convalescent plasma group and 80 of 465 (17.2%) patients in the placebo group had died (aOR, 1.04; 1/7 SI, 0.69-1.58). Interpretation: Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04362176; URL: www.clinicaltrials.gov
Self, Wesley H.; Wheeler, Allison P.; Stewart, Thomas G.; Schrager, Harry; Mallada, Jason; Thomas, Christopher B.; Cataldo, Vince D.; O'Neal, Hollis R.; Shapiro, Nathan I.; Higgins, Conor; Ginde, Adit A.; Chauhan, Lakshmi; Johnson, Nicholas J.; Henning, Daniel J.; Jaiswal, Stuti J.; Mammen, Manoj J.; Harris, Estelle S.; Pannu, Sonal R.; Laguio-Vila, Maryrose; El Atrouni, Wissam; de Wit, Marjolein; Hoda, Daanish; Cohn, Claudia S.; McWilliams, Carla; Shanholtz, Carl; Jones, Alan E.; Raval, Jay S.; and Mucha, Simon, "Neutralizing Covid-19 Convalescent Plasma In Adults Hospitalized With Covid-19: A Blinded, Randomized, Placebo-controlled Trial" (2022). School of Medicine Faculty Publications. 535.