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Clinical Trial
. 2025 May;97(5):e70349.
doi: 10.1002/jmv.70349.

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)

Edward N Janoff  1   2 , Mei-Chiung Shih  3   4 , Curtis Donskey  5   6 , Ilana Belitskaya-Levy  3 , Norbert Brau  7   8 , Maria C Rodriguez-Barradas  9 , Ernest Chan  5 , Peter Zimmerman  5 , Elliott K Miller  10 , Leroy B Vaughan  11 , J Daniel Markley  11 , Alexa M Goldberg  10 , Peruvemba Sriram  12 , Antonio Anzueto  13 , Lauren Uyeda  3 , Lisa Zehm  3 , Ashlea Wills  1 , Caitlin Hutchinson  1 , Lucas Jones  5   6 , Dianne Peterson  14 , Robert J Ringer  14 , Larry Dumont  15 , Theresa Gleason  16 , Robert A Bonomo  5   6 , Jeffrey L Curtis  17   18 , Sheldon T Brown  7   8 ; CURES‐1 Trials Consortium
Affiliations
Clinical Trial

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)

Edward N Janoff et al. J Med Virol. 2025 May.

Abstract

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.

Keywords: COVID‐19; convalescent plasma; hypoxemia; randomized controlled trial; respiratory failure; viral complexity.

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References

    1. Team CC‐R, “Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients With Coronavirus Disease 2019—United States, February 12–March 28, 2020,” MMWR: Morbidity and Mortality Weekly Report 69, no. 13 (2020): 382–386.
    1. W. J. Guan, Z. Y. Ni, Y. Hu, et al., “Clinical Characteristics of Coronavirus Disease 2019 in China,” New England Journal of Medicine 382, no. 18 (2020): 1708–1720.
    1. M. Jamal, H. I. Bangash, M. Habiba, et al., “Immune Dysregulation and System Pathology in COVID‐19,” Virulence 12, no. 1 (2021): 918–936.
    1. G. Li and E. De Clercq, “Therapeutic Options for the 2019 Novel Coronavirus (2019 nCoV),” Nature Reviews Drug Discovery 19, no. 3 (2020): 149–150.
    1. X. Xia, K. Li, L. Wu, et al., “Improved Clinical Symptoms and Mortality Among Patients With Severe or Critical COVID‐19 After Convalescent Plasma Transfusion,” Blood 136, no. 6 (2020): 755–759.

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