From a January 2021 editorial in NEJM:
Considering the number of SARS-CoV-2 infections, the paucity of treatment options, and the enthusiasm for and controversy about convalescent plasma, a high-quality, multicenter, randomized, controlled trial is most welcome. Libster and colleagues now report in the Journal the results of a well-executed trial of early convalescent plasma in older adult patients in whom symptomatic SARS-CoV-2 infection was diagnosed with the use of a polymerase-chain-reaction assay. In this double-blind trial, 250 ml of convalescent plasma with an IgG titer greater than 1:1000 against SARS-CoV-2 spike (S) protein was compared with saline placebo in patients who were 65 to 74 years of age and had prespecified coexisting conditions and in patients who were 75 years of age or older with or without coexisting conditions.
The patients received convalescent plasma or placebo less than 72 hours after symptom onset. In the intention-to-treat population, a primary end-point event (progression to predefined severe disease during follow-up) occurred in 16% (13 of 80 patients) and 31% (25 of 80 patients) of the well-matched convalescent plasma and placebo groups, respectively. A dose-dependent effect relative to the antibody titers after infusion was observed, and this effect was larger after the exclusion of 6 patients who had a primary end-point event before infusion. The benefits of convalescent plasma with respect to the secondary end points were consistent with those associated with the primary end point. No serious adverse events were observed. The authors conclude that “early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19.” Even before the current trial, the EUA [emergency use authorization] emphasized the potential advantages of early therapy with high-titer convalescent plasma. Unfortunately, a direct comparison of antibody levels in the current trial with assays specified in the FDA EUA is not available. Antibody titers in the recipients at enrollment were not provided, so no comment can be made about the usefulness of seroreactivity in patients as a criterion for convalescent plasma use.
At this time, convalescent plasma should be reserved for patients in whom the duration, severity, and risk of progression of illness are similar to those in the patients in this trial. Younger high-risk patients (and certain immunodeficient patients) with these disease characteristics should be considered as well.