Early Safety Indicators of COVID-19 ConvalescentPlasma in 5,000 Patients

Joyner, M.; Wright, R. S.; Fairweather, D.; Senefeld, J.; Bruno, K.; Klassen, S.; Carter, R.; Klompas, A.; Wiggins, C.; Shepherd, J. R.; Rea, R.; Whelan, E.; Clayburn, A.; Spiegel, M.; Johnson, P.; Lesser, E.; Baker, S.; Larson, K.; Ripoll Sanz, J.; Andersen, K.; Hodge, D.; Kunze, K.; Buras, M.; Vogt, M.; Herasevich, V.; Dennis, J.; Regimbal, R.; Bauer, P.; Blair, J.; van Buskirk, C.; Winters, J.; Stubbs, J.; Paneth, N.; Casadevall, A.

Background: Convalescent plasma is the only antibody based therapy currently available for COVID-19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. Methods: Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. Results: The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n=4), transfusion-associated circulatory overload (TACO; n=7), transfusion-related acute lung injury (TRALI; n=11), and severe allergic transfusion reactions (n=3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. Conclusion: Given the deadly nature of COVID-19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.