Early safety indicators of COVID-19 convalescent plasma in 5000 patients

Abstract

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). 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 5000 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), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (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 7-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.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Keywords: COVID-19; Drug therapy; Immunoglobulins.

Figure 1. Participation in the US COVID-19 convalescent plasma expanded access program, including data extracted on May 11, 2020.

(A) Choropleth map displaying the number of cumulatively enrolled patients in the expanded access program (EAP) within each state of the contiguous US, with lower enrollment values displayed in a lighter hue of blue and higher enrollment values displayed in a darker hue of blue. Registered acute care facilities are represented as yellow circles, with larger circles indicating greater numbers of registered facilities within the metropolitan area of a city. The choropleth map does not display data from noncontiguous US locations, including registered facilities in Puerto Rico, Hawaii, Alaska, Guam, and Northern Mariana Islands. (B) The chronological line charts represent the cumulative number of enrolled patients (blue line) and the cumulative number of patients that have received a COVID-19 convalescent plasma transfusion (yellow line). The chronological bar charts represent analogous values — the number of enrolled patients (blue bars) and number of patients that have received a COVID 19 convalescent plasma transfusion (yellow bars) by day. The difference between the blue and yellow bars highlights a fulfillment gap in COVID-19 convalescent plasma, which was most acute at the onset of the EAP and has substantially improved.