Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19
MD, MPH Wesley H Self, MD Allison P Wheeler, PhD; Thomas G Stewart, MD Harry Schrager, PharmD, BCIDP Jason Mallada, MD Christopher B Thomas, MD Vince D Cataldo, Hollis R O’neal, MD, MPH Nathan I Shapiro, BS Conor Higgins, MD, MPH Adit A Ginde, MD Lakshmi Chauhan, MD Nicholas J Johnson, MD, MPH Daniel J Henning, MD Stuti J Jaiswal, PhD Manoj J Mammen, MD Estelle S Harris, MD Sonal R Pannu, MD Maryrose Laguio-Vila, Wissam El Atrouni, MD Marjolein De Wit, MD Daanish Hoda, MD Claudia S Cohn, MD Carla Mcwilliams, MD Carl Shanholtz, MD Alan E Jones, MD Jay S Raval, MD Simon Mucha, MD, MPH Tina S Ipe, MD Xian Qiao, MD Stephen J Schrantz, MD Aarthi Shenoy, MD Richard D Fremont, BS Eric J Brady, PhD Robert H Carnahan, MD James D Chappell, PhD James E Crowe Jr, MD Mark R Denison, MD Pavlo Gilchuk, PhD Laura J Stevens, MS Rachel E Sutton, MD Isaac Thomsen, MT Sandra M Yoder, BS Amanda J Bistran-Hall, MD Jonathan D Casey, PhD Christopher J Lindsell, MS Li Wang, MBA Jill M Pulley, PhD Jillian P Rhoads, MD Gordon R Bernard, MD Todd W Rice
Chest, doi:10.1016/j.chest.2022.06.029
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 ¼ 487) or placebo (n ¼ 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.
In each plot, the convalescent plasma group is represented by blue lines and the placebo group by red lines. The top set of lines are Kaplan-Meier survival plots. The bottom set of lines denote the proportion of participants alive and discharged from the hospital. Patient disposition is represented by the three locations within the plot area: dead, represented by the area above the survival lines; alive and still in the hospital, represented by the area between the survival and discharge lines; and discharged from the hospital alive, represented by the area under the discharge lines. The proportion in each disposition state is denoted by the relative height of the region for each day. On study day 1, the vast majority of participants were alive and in the hospital (middle region). Over time, the proportion of participants in the alive and discharged state (lower region) and dead state (upper region) increases, which gives rise to the "funnel" shape of the plot. Participants could move from either in-hospital or discharged states to the dead state. Patients were followed up via medical records and telephone follow-up until 28 days following study infusion. Patients lost to follow-up were included in the risk-set for the portion of days for which disposition was known. A patient was considered discharged from the hospital once discharged from the index hospitalization; re-hospitalizations were not considered in this analysis. In model-based estimates of treatment..
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