Microbiology Spectrum (Jan 2024)
COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial
- Feben Habtehyimer,
- Xianming Zhu,
- Andrew D. Redd,
- Kelly A. Gebo,
- Alison G. Abraham,
- Eshan U. Patel,
- Oliver Laeyendecker,
- Thomas J. Gniadek,
- Reinaldo E. Fernandez,
- Owen R. Baker,
- Malathi Ram,
- Edward R. Cachay,
- Judith S. Currier,
- Yuriko Fukuta,
- Jonathan M. Gerber,
- Sonya L. Heath,
- Barry Meisenberg,
- Moises A. Huaman,
- Adam C. Levine,
- Aarthi Shenoy,
- Shweta Anjan,
- Janis E. Blair,
- Daniel Cruser,
- Donald N. Forthal,
- Laura L. Hammitt,
- Seble Kassaye,
- Giselle S. Mosnaim,
- Bela Patel,
- James H. Paxton,
- Jay S. Raval,
- Catherine G. Sutcliffe,
- Matthew Abinante,
- Kevin S. Oei,
- Valerie Cluzet,
- Marie Elena Cordisco,
- Benjamin Greenblatt,
- William Rausch,
- David Shade,
- Amy L. Gawad,
- Sabra L. Klein,
- Andrew Pekosz,
- Shmuel Shoham,
- Arturo Casadevall,
- Evan M. Bloch,
- Daniel Hanley,
- Aaron A. R. Tobian,
- David J. Sullivan
Affiliations
- Feben Habtehyimer
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Xianming Zhu
- Department of Pathology, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Andrew D. Redd
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Kelly A. Gebo
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Alison G. Abraham
- Department of Epidemiology, University of Colorado, Anschutz Medical Campus , Aurora, Colorado, USA
- Eshan U. Patel
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Oliver Laeyendecker
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Baltimore, Maryland, USA
- Thomas J. Gniadek
- Department of Pathology and Laboratory Medicine, Northshore University Health System , Evanston, Illinois, USA
- Reinaldo E. Fernandez
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Owen R. Baker
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Malathi Ram
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Edward R. Cachay
- Department of Medicine, Division of Infectious Diseases, University of California, San Diego , San Diego, California, USA
- Judith S. Currier
- Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles , Los Angeles, California, USA
- Yuriko Fukuta
- Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine , Houston, Texas, USA
- Jonathan M. Gerber
- Department of Medicine, Division of Hematology and Oncology, University of Massachusetts Chan Medical School , Worcester, Massachusetts, USA
- Sonya L. Heath
- Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham , Birmingham, Alabama, USA
- Barry Meisenberg
- Department of Medicine and Research Institute of Luminis Health , Annapolis, Maryland, USA
- Moises A. Huaman
- Department of Medicine, Division of Infectious Diseases, University of Cincinnati , Cincinnati, Ohio, USA
- Adam C. Levine
- Department of Emergency Medicine, Warren Alpert Medical School of Brown University , Providence, Rhode Island, USA
- Aarthi Shenoy
- Department of Medicine, Division of Hematology and Oncology, MedStar Washington Hospital Center , Washington, DC, USA
- Shweta Anjan
- Department of Medicine, Division of Infectious Diseases, University of Miami, Miller School of Medicine , Miami, Florida, USA
- Janis E. Blair
- Department of Medicine, Division of Infectious Diseases, Mayo Clinic Hospital , Phoenix, Arizona, USA
- Daniel Cruser
- Department of Pathology, Nuvance Health Vassar Brothers Medical Center , Poughkeepsie, New York, USA
- Donald N. Forthal
- Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California, USA
- Laura L. Hammitt
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Seble Kassaye
- Division of Infectious Diseases, Georgetown University Medical Center , Washington, DC, USA
- Giselle S. Mosnaim
- Department of Medicine, Division of Allergy and Immunology, Northshore University Health System , Evanston, Illinois, USA
- Bela Patel
- Department of Medicine, Divisions of Pulmonary and Critical Care Medicine, University of Texas Health Science Center , Houston, Texas, USA
- James H. Paxton
- Department of Emergency Medicine, Wayne State University , Detroit, Michigan, USA
- Jay S. Raval
- Department of Pathology, University of New Mexico , Albuquerque, New Mexico, USA
- Catherine G. Sutcliffe
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Matthew Abinante
- Ascada Research , Fullerton, California, USA
- Kevin S. Oei
- Ascada Research , Fullerton, California, USA
- Valerie Cluzet
- Department of Infectious Disease, Nuvance Health Vassar Brothers Medical Center , Poughkeepsie, New York, USA
- Marie Elena Cordisco
- Nuvance Health Danbury Hospital , Danbury, Connecticut, USA
- Benjamin Greenblatt
- Nuvance Health Norwalk Hospital , Norwalk, Connecticut, USA
- William Rausch
- Nuvance Health Danbury Hospital , Danbury, Connecticut, USA
- David Shade
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Amy L. Gawad
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Sabra L. Klein
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Andrew Pekosz
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Shmuel Shoham
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Arturo Casadevall
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- Evan M. Bloch
- Department of Pathology, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Daniel Hanley
- Department of Neurology, Brain Injury Outcomes Division, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- Aaron A. R. Tobian
- Department of Pathology, Johns Hopkins School of Medicine, Johns Hopkins University , Baltimore, Maryland, USA
- David J. Sullivan
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland, USA
- DOI
- https://doi.org/10.1128/spectrum.03286-23
- Journal volume & issue
-
Vol. 12,
no. 1
Abstract
ABSTRACT Early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. Wilcoxon rank sum tests were used to evaluate the difference between early (transfused within 5 days of symptom onset) CCP vs early control plasma and late (transfused 6–9 days after symptom onset) CCP vs late control plasma at each visit. Linear mixed-effect models were used to assess the difference in the slope of cytokine change. Median cytokine and chemokine levels were similar between the early CCP and early control groups pre-transfusion. At the day 14 visit, only the median IL-6 (P = 0.014) and IL-16 (P = 0.036) levels were lower in the early CCP group compared to the early control group, but these differences were not statistically significant after correcting for multiple comparisons (requiring P < 0.0024). IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group (P < 0.001). No difference was observed in the slope of cytokine change from screening to day 90 between early CCP and early control groups. Late control and late CCP arms showed similar cytokine and chemokine levels through study follow-up. One mechanism by which early CCP transfusion reduces hospitalization may be by decreasing IL-6 levels, as the reduction is associated with better recovery from COVID-19. IMPORTANCE This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.
Keywords
