Post-trial follow-up after a randomized clinical trial of COVID-19 convalescent plasma

Abstract

Background: COVID-19 convalescent plasma (CP) proved to be a safe acute intervention, however, the long-term clinical effects of COVID-19 CP are to date unknown. CP might have a prospective negative effect by down-regulating the inflammatory response suppressing antibody formation and promoting autoantibodies against interferons. Our objective was to establish the long-term safety profile of COVID-19 CP and determine if its administration increases the risk for further respiratory infections in older adults. Methods: All participants included in the intention to treat analysis of a randomized clinical trial evaluating the efficacy of COVID-19 CP in older adults were invited to participate in this post-trial follow-up study. Patients were strictly followed for at least 6 months after randomization. The primary endpoint was the number of patients with clinically confirmed acute respiratory infections (ARIs). Secondary endpoints included all-cause mortality, time to first respiratory infection, SARS-CoV-2 re-infection, adverse events, and persistence of COVID-19 symptoms after initial infection. Results: 142 patients were included in the study (total retention rate=92.8%). The mean age was 77.2 years (SD=8.6) and the median duration of follow-up was 10.4 months (IQR=1.63), with no differences among groups. 20 patients had a clinically confirmed ARI during the study. No differences were observed between groups in the proportion of ARIs (CP=11/72 and Placebo=9/70, p-value=0.678) and in the probability of ARI-free survival between groups (log-rank test p-value=0.63). No differences emerged when comparing groups regarding secondary endpoints. Conclusions: COVID-19 convalescent plasma remains a safe intervention without increasing the risk of acute respiratory infection or other clinical consequences in the long term.