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 ShenoyShweta 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalMicrobiology Spectrum
Volume12
Issue number1
DOIs
StatePublished - Jan 2024

Keywords

  • COVID-19
  • COVID-19 serotherapy
  • SARS-CoV-2
  • chemokines
  • convalescent plasma
  • cytokines
  • randomized trial

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • Microbiology (medical)
  • Infectious Diseases
  • Genetics
  • Physiology
  • Cell Biology
  • Ecology

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