High Dose Convalescent Plasma in COVID-19: Results from the randomized Trial CAPSID

Koerper, S.; Weiss, M.; Zickler, D.; Wiesmann, T.; Zacharowski, K.; Corman, V. M.; Gruener, B.; Ernst, L.; Spieth, P.; Lepper, P. M.; Bentz, M.; Zinn, S.; Paul, G.; Kalbhenn, J.; Dollinger, M.; Rosenberger, P.; Kirschning, T.; Thiele, T.; Appl, T.; Mayer, B.; Schmidt, M.; Drosten, C.; Wulf, H.; Kruse, J. M.; Jungwirth, B.; Seifried, E.; Schrezenmeier, H.

Rationale: COVID-19 convalescent plasma (CCP) has been considered a treatment option in COVID-19. Objectives:: To assess the efficacy of 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. Primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. The trial is registered: clinicaltrials.gov #NCT04433910. Measurements and main results: The primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The median time to clinical improvement was 26 days (IQR 15-not reached (n.r.)) in the CCP group and 66 days (IQR 13-n.r.) in the control group (p=0.27). Median time to discharge from hospital was 31 days (IQR 16-n.r.) in the CCP and 51 days (IQR 20-n.r.) 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% (versus 32.1%), with a shorter interval to clinical improvement, shorter time to hospital discharge and better survival compared to the control group. Conclusion: CCP added to standard treatment did not result in a significant difference in the primary and secondary outcomes. A pre-defined subgroup analysis showed a significant benefit for CCP among those who received a larger amount of neutralizing antibodies. Primary Funding Source: Bundesministerium fuer Gesundheit