Early Convalescent Plasma Therapy and Mortality Among US Veterans Hospitalized With Nonsevere COVID-19: An Observational Analysis Emulating a Target Trial

Abstract Background Early convalescent plasma transfusion may reduce mortality in patients with nonsevere coronavirus disease 2019 (COVID-19). Methods This study emulates a (hypothetical) target trial using observational data from a cohort of US veterans admitted to a Department of Veterans Affairs (VA) facility between 1 May and 17 November 2020 with nonsevere COVID-19. The intervention was convalescent plasma initiated within 2 days of eligibility. Thirty-day mortality was compared using cumulative incidence curves, risk differences, and hazard ratios estimated from pooled logistic models with inverse probability weighting to adjust for confounding. Results Of 11 269 eligible person-trials contributed by 4755 patients, 402 trials were assigned to the convalescent plasma group. Forty and 671 deaths occurred within the plasma and nonplasma groups, respectively. The estimated 30-day mortality risk was 6.5% (95% confidence interval [CI], 4.0%–9.7%) in the plasma group and 6.2% (95% CI, 5.6%–7.0%) in the nonplasma group. The associated risk difference was 0.30% (95% CI, −2.30% to 3.60%) and the hazard ratio was 1.04 (95% CI, .64–1.62). Conclusions Our target trial emulation estimated no meaningful differences in 30-day mortality between nonsevere COVID-19 patients treated and untreated with convalescent plasma. Clinical Trials Registration. NCT04545047. This study used electronic health record data to emulate a target trial of early COVID-19 convalescent plasma and 30-day mortality risk. No differences in mortality risk were found between patients with nonsevere COVID-19 who were treated and untreated with plasma.