The Journal of Clinical Investigation
C L I N I C A L M E D I C I N E, Sixten Körper, Manfred Weiss, Daniel Zickler, Thomas Wiesmann, Kai Zacharowski, Victor M Corman, Beate Grüner, Lucas Ernst, Peter Spieth, Philipp M Lepper, Martin Bentz, Sebastian Zinn, Gregor Paul, Johannes Kalbhenn, Matthias M Dollinger, Peter Rosenberger, Thomas Kirschning, Thomas Thiele, Thomas Appl, Benjamin Mayer, Michael Schmidt, Christian Drosten, Hinnerk Wulf, Jan Matthias Kruse, Bettina Jungwirth, Erhard Seifried, Hubert Schrezenmeier
doi:10.1172/JCI152264DS1).
BACKGROUND. COVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.
METHODS. Patients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.
RESULTS. The primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group. CONCLUSION. CCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies. TRIAL REGISTRATION. ClinicalTrials.gov NCT04433910.
Author contributions HS and SK wrote study protocol, coordinated the study, analyzed and interpreted data, and wrote the manuscript. HS, SK, and ES applied for funding. HS and ES were the lead investigators. MW, DZ, TW, KZ, BG, LE, PS, PML, MB, SZ, GP, JK, MMD, PR, TK, TT, HW, JMK, and BJ performed patient care and data collection. VMC and CD performed analysis of SARS-CoV-2 antibodies. MS performed SARS-CoV-2 PCR. TA managed the project. BM performed statistical analysis. All authors approved the manuscript.
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