Impact of High‐Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS‐CoV‐2 Infection: VA CoronavirUs Research and Efficacy Studies‐1 (VA CURES‐1)
In the initial absence of proven therapies, empirical COVID-19 convalescent plasma (CCP) was rapidly introduced for individuals hospitalized for COVID-19. Seventy-five participants were randomized from November 2020 to June 2021 in a double-blind, multi-site, placebo-controlled, randomized trial (VA CURES-1) evaluating the impact of CCP vs. saline in Veterans hospitalized with COVID-19 with hypoxemia. The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 29. We analyzed clinical outcomes, nasal viral RNA, plasma cytokines and viral evolution over time. Among 40 participants receiving saline and 35 receiving CCP with high neutralizing titers (median 1:1420), the percent reaching the primary outcome was similar (10%), as were time to clinical recovery and to nasal viral clearance. By whole genome sequencing, viral molecular complexity evolved pre- to posttreatment more frequently in recipients of saline vs. CCP (4 of 7 (57.1%) vs. 1 of 4 (25%), respectively), based on numbers of mixed allele positions. Numbers of amino acid-changing, non-synonymous mutations in the spike protein were greater in saline vs. CCP recipients. Both outcomes suggested purifying selection (reduced overall viral infection complexity) following CCP. In conclusion, convalescent plasma showed no significant clinical impact but may influence SARS-CoV-2 complexity. Trial Registration: ClinicalTrials.gov Identifier: NCT04539275.
Authors
- Robert A. Bonomo (ORCID: https://orcid.org/0000-0002-3299-894X)
- Elliott K. Miller (ORCID: https://orcid.org/0000-0002-7395-9197)
- Lucas D. Jones (ORCID: https://orcid.org/0000-0002-0350-6694)
- Maria C. Rodriguez‐Barradas (ORCID: https://orcid.org/0000-0003-2446-2667)
- Ilana Belitskaya‐Lévy
- Leroy Vaughan
- Peter A. Zimmerman (ORCID: https://orcid.org/0000-0002-5349-4513)
- E. Ricky Chan (ORCID: https://orcid.org/0000-0001-9277-5329)
- Edward N. Janoff (ORCID: https://orcid.org/0000-0003-2702-5729)
- Caitlin Hutchinson
- Lisa Zehm (ORCID: https://orcid.org/0000-0002-2269-2381)
- Jeffrey L. Curtis (ORCID: https://orcid.org/0000-0001-5191-4847)
- Antonio Anzueto (ORCID: https://orcid.org/0000-0002-7007-588X)
- Curtis J. Donskey (ORCID: https://orcid.org/0000-0003-0990-4498)
- Lauren Uyeda (ORCID: https://orcid.org/0000-0001-9213-0280)
- Sheldon T. Brown (ORCID: https://orcid.org/0000-0002-4563-4854)
- Ashlea Wills
- Larry J. Dumont (ORCID: https://orcid.org/0000-0002-1715-0748)
- Dianne Peterson
- Norbert Bräu
- J. Daniel Markley (ORCID: https://orcid.org/0009-0002-7644-9720)
- Peruvemba Sriram (ORCID: https://orcid.org/0000-0002-6103-3573)
- Robert J. Ringer
- Alexa M. Goldberg (ORCID: https://orcid.org/0009-0000-0519-5247)
- Mei‐Chiung Shih
- Theresa Gleason
Institutions
- Michael E. DeBakey VA Medical Center (US)
- The University of Texas at San Antonio Health Science Center (US)
- Baylor College of Medicine (US)
- Virginia Commonwealth University (US)
- University of Michigan (US)
- University of Florida (US)
- VA Ann Arbor Healthcare System (US)
- Louis Stokes Cleveland VA Medical Center (US)
- James J. Peters VA Medical Center (US)
- North Florida/South Georgia Veterans Health System (US)
- Vitalant (US)
- South Texas Veterans Health Care System (US)
- University School (US)
- Case Western Reserve University (US)
- University of Colorado Denver (US)
- Florida College (US)
- Stanford University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Journal of Medical Virology
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1002/jmv.70349
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Veterans Affairs
- Office of Research and Development