Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Convalescent Plasma Hesitancy cost lives?

The US Food and Drug Administration (FDA) authorized treatment of hospitalized COVID-19 patients with Convalescent Plasma (CCP) via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to the use of CCP in some 500,000 patients during the first year of the pandemic. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data over the course of the year. CCP usage per admission peaked after issuance of the EUA, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, following reports of randomized controlled trials that failed to show clear benefit from CCP, usage/admissions declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (Pearsons correlation coefficient of -0.5176 with P = 0.00242) between CCP usage/hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, prevalence of variants, and age of patients could not explain these findings. We estimate that the retreat from CCP usage, a phenomenon we termed plasma hesitancy, might have resulted in 29,000 to 36,000 excess deaths in the period from mid-November 2020 to February 2021. These results highlight the need for additional studies to ascertain the variables associated with efficacy and/or provide other explanations for the robust relationships observed in this study.

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

BackgroundConvalescent 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. MethodsThus, 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. ResultsThe 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%. ConclusionGiven 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. Brief SummaryAfter transfusion of COVID-19 convalescent plasma in 5,000 patients, the incidence of serious adverse events was <1% and the seven-day incidence of mortality was 14.9%.