Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials

Moises A Huaman¹, Jay S Raval², James H Paxton³, Giselle S Mosnaim⁴, Bela Patel⁵, Shweta Anjan⁶, Barry R Meisenberg⁷, Adam C Levine⁸, Christi E Marshall⁹, Anusha Yarava¹⁰, Aarthi G Shenoy¹¹, Sonya L Heath¹², Judith S Currier¹³, Yuriko Fukuta¹⁴, Janis E Blair¹⁵, Emily S Spivak¹⁶, Joann R Petrini¹⁷, Patrick B Broderick¹⁸, William Rausch¹⁷, MarieElena Cordisco¹⁷, Jean Hammel¹⁹, Benjamin Greenblatt¹⁹, Valerie C Cluzet²⁰, Daniel Cruser²⁰, Kevin Oei²¹, Matthew Abinante²¹, Laura L Hammitt²², Catherine G Sutcliffe²², Donald N Forthal²³, Martin S Zand²⁴, Edward R Cachay²⁵, Seble G Kassaye²⁶, Malathi Ram²², Ying Wang¹⁰, Piyali Das¹⁰, Karen Lane¹⁰, Nichol A McBee¹⁰, Amy L Gawad¹⁰, Nicky Karlen¹⁰, Daniel E Ford²⁷, Oliver Laeyendecker²⁸, Andrew Pekosz²⁹, Sabra L Klein²⁹, Stephan Ehrhardt³⁰, Bryan Lau³⁰, Sheriza N Baksh³⁰, David M Shade³⁰, Arturo Casadevall²⁹, Daniel F Hanley¹⁰, Jiangda Ou¹⁰, Thomas J Gniadek³¹, Alyssa Ziman³², Shmuel Shoham³³, Kelly A Gebo³³, Evan M Bloch⁹, Aaron A R Tobian⁹, David J Sullivan²⁹, Jonathan M Gerber³⁴

Affiliations

¹ Department of Internal Medicine, Division of Infectious Diseases, University of Cincinnati, Cincinnati, Ohio, USA.
² Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
³ Department of Emergency Medicine, Wayne State University, Detroit, Michigan, USA.
⁴ Department of Medicine, Division of Allergy and Immunology, NorthShore University Health System, Evanston, Illinois, USA.
⁵ Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center, Houston, Texas, USA.
⁶ Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁷ Luminis Health, Annapolis, Maryland, USA.
⁸ Department of Emergency Medicine, Rhode Island Hospital & Brown University, Providence, Rhode Island, USA.
⁹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Neurology, Brain Injury Outcomes Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ Department of Medicine, Division of Hematology and Oncology, MedStar Washington Hospital Center, DC, USA.
¹² Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹³ Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, USA.
¹⁴ Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA.
¹⁵ Department of Medicine, Division of Infectious Diseases, Mayo Clinic Hospital, Phoenix, Arizona, USA.
¹⁶ Department of Medicine, Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹⁷ Nuvance Health, Danbury, Connecticut, USA.
¹⁸ Nuvance Health Danbury Hospital, Danbury, Connecticut, USA.
¹⁹ Nuvance Health Norwalk Hospital, Norwalk, Connecticut, USA.
²⁰ Nuvance Health Vassar Brothers Medical Center, Poughkeepsie, New York, USA.
²¹ Ascada Research, Fullerton, California, USA.
²² Department of International Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
²³ Department of Medicine, Division of Infectious Diseases, University of California, Irvine, California, USA.
²⁴ Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA.
²⁵ Department of Medicine, Division of Infectious Diseases, University of California, San Diego, California, USA.
²⁶ Department of Medicine, Division of Infectious Diseases, Georgetown University Medical Center, DC, USA.
²⁷ Institute for Clinical and Translational Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁸ The Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
²⁹ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
³⁰ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
³¹ Department of Pathology and Laboratory Medicine, NorthShore University Health System, Evanston, Illinois, USA.
³² Department of Pathology and Laboratory Medicine, Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
³³ Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³⁴ Department of Medicine, Division of Hematology and Oncology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.

PMID: 37534607
PMCID: PMC10720768
DOI: 10.1111/trf.17485

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials

Moises A Huaman et al. Transfusion. 2023 Sep.

. 2023 Sep;63(9):1639-1648.

doi: 10.1111/trf.17485. Epub 2023 Aug 3.

Authors

Affiliations

¹ Department of Internal Medicine, Division of Infectious Diseases, University of Cincinnati, Cincinnati, Ohio, USA.
² Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
³ Department of Emergency Medicine, Wayne State University, Detroit, Michigan, USA.
⁴ Department of Medicine, Division of Allergy and Immunology, NorthShore University Health System, Evanston, Illinois, USA.
⁵ Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center, Houston, Texas, USA.
⁶ Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁷ Luminis Health, Annapolis, Maryland, USA.
⁸ Department of Emergency Medicine, Rhode Island Hospital & Brown University, Providence, Rhode Island, USA.
⁹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Neurology, Brain Injury Outcomes Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ Department of Medicine, Division of Hematology and Oncology, MedStar Washington Hospital Center, DC, USA.
¹² Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹³ Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, USA.
¹⁴ Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA.
¹⁵ Department of Medicine, Division of Infectious Diseases, Mayo Clinic Hospital, Phoenix, Arizona, USA.
¹⁶ Department of Medicine, Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹⁷ Nuvance Health, Danbury, Connecticut, USA.
¹⁸ Nuvance Health Danbury Hospital, Danbury, Connecticut, USA.
¹⁹ Nuvance Health Norwalk Hospital, Norwalk, Connecticut, USA.
²⁰ Nuvance Health Vassar Brothers Medical Center, Poughkeepsie, New York, USA.
²¹ Ascada Research, Fullerton, California, USA.
²² Department of International Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
²³ Department of Medicine, Division of Infectious Diseases, University of California, Irvine, California, USA.
²⁴ Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA.
²⁵ Department of Medicine, Division of Infectious Diseases, University of California, San Diego, California, USA.
²⁶ Department of Medicine, Division of Infectious Diseases, Georgetown University Medical Center, DC, USA.
²⁷ Institute for Clinical and Translational Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁸ The Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
²⁹ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
³⁰ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
³¹ Department of Pathology and Laboratory Medicine, NorthShore University Health System, Evanston, Illinois, USA.
³² Department of Pathology and Laboratory Medicine, Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
³³ Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³⁴ Department of Medicine, Division of Hematology and Oncology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.

PMID: 37534607
PMCID: PMC10720768
DOI: 10.1111/trf.17485

Abstract

Background: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

Study design and methods: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders.

Results: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications.

Discussion: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.

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Conflict of interest statement

Conflicts of interest

MAH: contracts from Gilead Sciences Inc, Insmed Inc, AN2 Therapeutics, Inc to the University of Cincinnati, outside the submitted work. TG- Paid consultant and employee of Fenwal, a Fresenius Kabi company; AC- Scientific Advisory Board of Sabtherapeutics (cow-derived human immunoglobulins COVID-19 treatment and other infectious diseases) and Ortho Diagnostics Speakers Bureau; EB- member of the FDA Blood Products Advisory Committee; SS reports research grants; F2G, Cidara, Ansun, Zeteo, Emergent Biosolutions: personal fees as consultant, speaker, advisory board, data safety monitoring board member; Celltrion, Adagio, Immunome, Adamis, Karyopharm, Intermountain Health, Karius, Avir Pharma; CGS: Centers for Disease Control and Prevention, Merck: Research Grants. All other authors report no relevant disclosures.

References

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Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials

Affiliations

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous