Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial

Authors

Wesley H. Self, Vanderbilt Institute for Clinical and Translational Research and Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN. Electronic address: wesley.self@vumc.org
Allison P. Wheeler, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.
Thomas G. Stewart, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
Harry Schrager, Department of Medicine, Tufts School of Medicine, Newton-Wellesley Hospital, Newton, MA
Jason Mallada, Department of Pharmacy, Newton-Wellesley Hospital, Massachusetts College of Pharmacy and Health Sciences, Newton, MA
Christopher B. Thomas, Division of Pulmonary and Critical Care, Louisiana State University Health-Sciences Center, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
Vince D. Cataldo, Division of Hematology and Oncology, Louisiana State University Health-Sciences Center, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
Hollis R. O'Neal, Division of Pulmonary and Critical Care, Louisiana State University Health-Sciences Center, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
Nathan I. Shapiro, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA
Conor Higgins, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA
Adit A. Ginde, Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO
Lakshmi Chauhan, Department of Medicine, University of Colorado School of Medicine, Aurora, CO
Nicholas J. Johnson, Department of Emergency Medicine and Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA
Daniel J. Henning, Department of Emergency Medicine, University of Washington, Seattle, WA
Stuti J. Jaiswal, Division of Hospital Medicine, Scripps Clinic, Scripps Research Translational Institute, The Scripps Research Institute, La Jolla, CA
Manoj J. Mammen, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo, Buffalo, NY
Estelle S. Harris, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah, Salt Lake City, U
Sonal R. Pannu, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH
Maryrose Laguio-Vila, Department of Internal Medicine, Division of Infectious Disease, Rochester General Hospital, Rochester, NY
Wissam El Atrouni, Division of Infectious Diseases, Department of Internal Medicine, The University of Kansas Medical Center, Kansas City, KS
Marjolein de Wit, Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
Daanish Hoda, Oncology Clinical Program, Intermountain Healthcare, Murray, U
Claudia S. Cohn, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
Carla McWilliams, Department of Infectious Disease, Cleveland Clinic Florida Weston, Weston, FL
Carl Shanholtz, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
Alan E. Jones, Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS
Simon Mucha, Department of Critical Care, Respiratory Institute, Cleveland Clinical Health System, Cleveland, OH.
Tina S. Ipe, Department of Pathology and Laboratory Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
Xian Qiao, Sentara Pulmonary, Critical Care, and Sleep Specialists, Sentara Health, Sentara Norfolk General Hospital, Eastern Virginia Medical School, Norfolk, VA
Stephen J. Schrantz, cSentara Pulmonary, Critical Care, and Sleep Specialists, Sentara Health, Sentara Norfolk General Hospital, Eastern Virginia Medical School, Norfolk, VA
Aarthi Shenoy, cSentara Pulmonary, Critical Care, and Sleep Specialists, Sentara Health, Sentara Norfolk General Hospital, Eastern Virginia Medical School, Norfolk, VA
Richard D Fremont, Department of Medicine, Meharry Medical College, Nashville, TN
Eric J. Brady, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN
Robert H. Carnahan, Department of Pediatrics, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN; Department of Radiology, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN
James D. Chappell, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
James E. Crowe, Department of Pediatrics, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN; Department of Pediatrics, and Department of Pathology, Microbiology, and Immunology, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN
Mark R. Denison, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
Pavlo Gilchuk, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN
Laura J. Stevens, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
Rachel E. Sutton, Immunology and Molecular Pathogeneisis Program, Emory University, Atlanta, GA
Isaac Thomsen, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
Sandra M. Yoder, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN
Amanda J. Bistran-Hall, Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN
Jonathan D. Casey, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN
Christopher J. Lindsell, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
Li Wang, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
Jill M. Pulley, Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN
Jillian P. Rhoads, Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN
Gordon R. Bernard, Vanderbilt Institute for Clinical and Translational Research and Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN
Todd W. Rice, Vanderbilt Institute for Clinical and Translational Research and Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN
Jay S. Raval, Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM

Document Type

Article

Publication Date

11-1-2022

Abstract

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.

Recommended Citation

Self WH, Wheeler AP, Stewart TG, Schrager H, Mallada J, Thomas CB, Cataldo VD, O'Neal HR Jr, Shapiro NI, Higgins C, Ginde AA, Chauhan L, Johnson NJ, Henning DJ, Jaiswal SJ, Mammen MJ, Harris ES, Pannu SR, Laguio-Vila M, El Atrouni W, de Wit M, Hoda D, Cohn CS, McWilliams C, Shanholtz C, Jones AE, Raval JS, Mucha S, Ipe TS, Qiao X, Schrantz SJ, Shenoy A, Fremont RD, Brady EJ, Carnahan RH, Chappell JD, Crowe JE Jr, Denison MR, Gilchuk P, Stevens LJ, Sutton RE, Thomsen I, Yoder SM, Bistran-Hall AJ, Casey JD, Lindsell CJ, Wang L, Pulley JM, Rhoads JP, Bernard GR, Rice TW; Passive Immunity Trial for Our Nation (PassITON) Investigators. Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial. Chest. 2022 Nov;162(5):982-994. doi: 10.1016/j.chest.2022.06.029. Epub 2022 Jul 1. PMID: 35780813; PMCID: PMC9247217.