Deployment of convalescent plasma for the prevention and treatment of COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., "convalescent") plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East respiratory syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads, and improved survival. Globally, blood centers have robust infrastructure for undertaking collections and constructing inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections, and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs. treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, including evidence of benefit, regulatory considerations, logistical work flow, and proposed clinical trials, as scale-up is brought underway to mobilize this critical resource.

Conflict of interest statement

Conflict of interest: EMB is a member of the FDA Blood Products Advisory Committee.

Figures

Figure 1. Convalescent plasma collections workflow.

EUA, Emergency Use Authorization; TTI, transfusion-transmitted infection.

Figure 2. Mortality risk with SARS–CoV-2 convalescent plasma versus control by age, reproductive number, projected efficacy of intervention, and time.

Fatalities from SARS-CoV-2 were estimated by age groups assuming moderate and high R0 scenarios over 100 (d = 100) or 365 (d = 365) days. We calculated the number of averted deaths from treatment per 1,000 individuals for a range of treatment efficacy: (A) 25%, (B) 50%, and (C) 75%. We estimated these values using simulated incidence values from multiple runs of the transmission model. Results are shown for the mean (shown as a point) and 95% quantile. The estimated probability of death from a plasma transfusion was conservatively set at 41/3.6 million (solid black vertical line) (49).