Convalescent plasma in COVID-19: Does use case matter?

A randomized controlled trial of convalescent plasma in severe COVID-19 shows no benefits. Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of individuals worldwide. One of the most severe manifestations of COVID-19 is severe pneumonia leading to respiratory failure and the need for intensive care. Endeavoring to improve morbidity and mortality has been key, and several interventions have been attempted to modify outcomes in this critically ill population. One of these interventions is convalescent plasma: plasma collected from individuals who have recovered from COVID-19 and have high titers of antibodies to SARS-CoV-2. Convalescent plasma has been postulated to confer protection and improve outcomes. Based on the results from several non-randomized and observational studies, convalescent plasma is currently being used for the treatment of COVID-19, especially in critically ill patients. However, Simonovich et al. published the results of a randomized controlled trial in hospitalized patients with severe COVID-19 pneumonia that questions this treatment. In the study, patients with severe COVID-19 pneumonia were randomized to receive convalescent plasma or placebo in addition to standard care to assess impact on a six-point ordinal clinical status scale ranging from total recovery to death, 30 days after the intervention. Overall, 228 patients were randomized to receive convalescent plasma and 105 to receive placebo in a 2:1 ratio. At 30 days, no significant difference was found between convalescent plasma and placebo for any clinical outcome, including mortality. Although this trial has some limitations, including a limited sample size and lower antibody titers than in the observational studies, the results call into question the widespread clinical practice of convalescent plasma treatment in patients with severe COVID-19 pneumonia. Does this mean that convalescent plasma has no utility? COVID-19 is a heterogeneous disease, and the manifestations and pathophysiology differ depending on the stage of disease. A non-peer reviewed preprint has shown that when infected individuals were randomized to early administration of high-titer convalescent plasma, COVID-19 progression was reduced. However, randomized controlled trials are ideally needed before any intervention becomes standard of care, and COVID-19 should be no exception.