Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial

Shmuel Shoham; Evan M Bloch; Arturo Casadevall; Daniel Hanley; Bryan Lau; Kelly Gebo; Edward Cachay; Seble G Kassaye; James H Paxton; Jonathan Gerber; Adam C Levine; Arash Naeim; Judith Currier; Bela Patel; Elizabeth S Allen; Shweta Anjan; Lawrence Appel; Sheriza Baksh; Paul W Blair; Anthony Bowen; Patrick Broderick; Christopher A Caputo; Valerie Cluzet; Marie Elena Cordisco; Daniel Cruser; Stephan Ehrhardt; Donald Forthal; Yuriko Fukuta; Amy L Gawad; Thomas Gniadek; Jean Hammel; Moises A Huaman; Douglas A Jabs; Anne Jedlicka; Nicky Karlen; Sabra Klein; Oliver Laeyendecker; Karen Lane; Nichol McBee; Barry Meisenberg; Christian Merlo; Giselle Mosnaim; Han-Sol Park; Andrew Pekosz; Joann Petrini; William Rausch; David M Shade; Janna R Shapiro; J Robinson Singleton; Catherine Sutcliffe; David L Thomas; Anusha Yarava; Martin Zand; Jonathan M Zenilman; Aaron A R Tobian; David J Sullivan

doi:10.1093/cid/ciac372

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial

Clin Infect Dis. 2023 Feb 8;76(3):e477-e486. doi: 10.1093/cid/ciac372.

Authors

Shmuel Shoham¹, Evan M Bloch², Arturo Casadevall³, Daniel Hanley⁴, Bryan Lau⁵, Kelly Gebo¹, Edward Cachay⁶, Seble G Kassaye⁷, James H Paxton⁸, Jonathan Gerber⁹, Adam C Levine¹⁰, Arash Naeim¹¹, Judith Currier¹¹, Bela Patel¹², Elizabeth S Allen¹³, Shweta Anjan¹⁴, Lawrence Appel¹, Sheriza Baksh⁵, Paul W Blair¹, Anthony Bowen¹, Patrick Broderick¹⁵, Christopher A Caputo³, Valerie Cluzet¹⁶, Marie Elena Cordisco¹⁷, Daniel Cruser¹, Stephan Ehrhardt⁵, Donald Forthal¹⁸, Yuriko Fukuta¹⁹, Amy L Gawad⁴, Thomas Gniadek²⁰, Jean Hammel²¹, Moises A Huaman²², Douglas A Jabs²³, Anne Jedlicka³, Nicky Karlen²⁴, Sabra Klein³, Oliver Laeyendecker²⁵, Karen Lane⁴, Nichol McBee⁴, Barry Meisenberg²⁶, Christian Merlo¹, Giselle Mosnaim²⁷, Han-Sol Park³, Andrew Pekosz³, Joann Petrini¹⁷, William Rausch¹⁷, David M Shade⁵, Janna R Shapiro³, J Robinson Singleton²⁸, Catherine Sutcliffe⁵, David L Thomas¹, Anusha Yarava⁴, Martin Zand²⁹, Jonathan M Zenilman¹, Aaron A R Tobian², David J Sullivan³

Affiliations

¹ Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁴ Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁶ Department of Medicine, Division of Infectious Diseases, University of California, San Diego, San Diego, California, USA.
⁷ Division of Infectious Diseases/Department of Medicine, Georgetown University Medical Center, Washington D.C, USA.
⁸ Department of Emergency Medicine, Wayne State University, Detroit, Michigan, USA.
⁹ Department of Medicine, Division of Hematology and Oncology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
¹⁰ Department of Emergency Medicine, Rhode Island Hospital/Brown University, Providence, Rhode Island, USA.
¹¹ Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, Los Angeles, California, USA.
¹² Department of Medicine, Division Critical Care Medicine, University of Texas Health, Houston, Texas, USA.
¹³ Department of Pathology, University of California, San Diego, San Diego, California, USA.
¹⁴ Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA.
¹⁵ Department of Emergency Medicine, Danbury Hospital, Danbury, Connecticut, USA.
¹⁶ Vassar Brothers Medical Center, Nuvance Health, Poughkeepsie, New York, USA.
¹⁷ Office of Clinical Trials, Nuvance Health, University of Vermont, Danbury, Connecticut, USA.
¹⁸ Department of Medicine, Division of Infectious Diseases, University of California, Irvine, Irvine, California, USA.
¹⁹ Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Department of Pathology, Northshore University Health System, Evanston, Illinois, USA.
²¹ Department of Emergency Medicine, Norwalk Hospital, Norwalk, Connecticut, USA.
²² Department of Medicine, Division of Infectious Diseases, University of Cincinnati, Cincinnati, Ohio, USA.
²³ Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁴ Mosaic Consulting Ltd., Israel.
²⁵ Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA.
²⁶ Department of Medicine, Luminis Health, Annapolis, Maryland, USA.
²⁷ Division of Allergy and Immunology, Department of Medicine, Northshore University Health System, Evanston, Illinois, USA.
²⁸ Department of Neurology, University of Utah, Salt Lake City, Utah, USA.
²⁹ Department of Medicine, University of Rochester, Rochester, New York, USA.

Abstract

Background: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection.

Results: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups.

Conclusions: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection.

Clinical trials registration: NCT04323800.

Keywords: COVID-19; SARS-CoV-2; convalescent plasma; post-exposure-prophylaxis; transfusion.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adolescent
Adult
COVID-19 Serotherapy
COVID-19* / prevention & control
Double-Blind Method
Humans
Immunization, Passive
Post-Exposure Prophylaxis
SARS-CoV-2*

Associated data

ClinicalTrials.gov/NCT04323800

Abstract

Publication types

MeSH terms

Associated data

Grants and funding