Results of an open-label, randomized controlled trial found that treatment with convalescent plasma was not associated with a decreased risk for intubation or death compared with standard care in patients hospitalized with COVID-19. In addition, transfusions of convalescent plasma with unfavorable antibody profiles may be associated an increased risk for poor clinical outcomes. These findings were published in Nature Medicine.
Between May 2020 and January 2021, patients (N=938) hospitalized with COVID-19 at 72 sites in Canada, the United States, and Brazil were randomly assigned in a 2:1 fashion to receive convalescent plasma (n=614) or standard care (n=307). Clinical outcomes of COVID-19 were assessed. In addition, the investigators performed a meta-analysis of convalescent plasma for the treatment of COVID-19.
Of patients included in the study, the median age was 69 (interquartile range [IQR], 58-79) years, 59% were men, median time since initial onset of symptoms was 8 (IQR, 5-10) days, and most patients were receiving corticosteroids at study enrollment (81.7%).
Intubation or death occurred among 32.4% of patients who received convalescent plasma and 28.0% of those who received standard care (relative risk [RR], 1.16; 95% CI, 0.94-1.43; P =.18).
At day 30, death occurred among 23.0% of patients who received convalescent plasma vs 20.5% of those who received standard care (RR, 1.12; 95% CI, 0.86-1.46; P =.40).
Compared with patients who received standard care, the rate of adverse events at day 30 was increased among those who received convalescent plasma (33.4% vs 26.4%; RR, 1.27; 95% CI, 1.02-1.57; P =.03). In addition, the rate of severe (42.3% vs 35.5%; RR, 1.19; 95% CI, 1.00-1.42; P =.05) and life-threatening (30.6% vs 24.1%; RR, 1.27; 95% CI, 1.01-1.60; P =.04) adverse events also was increased among patients who received convalescent plasma.
After stratification by subgroup, the investigators found no significant differences in outcomes of intubation or death among the intention-to-treat population.
There were 4 suppliers of convalescent plasma used in this study. For every 1-unit increase in the antibody-dependent cellular toxicity concentration there was a decreased risk for the potential harmful treatment effect (odds ratio [OR], 0.66; 95% CI, 0.50-0.87). A similar trend was observed for serum neutralization (OR, 0.74; 95% CI, 0.57-0.95). For content of immunoglobulin G against the transmembrane spike protein, however, the risk for a potential harmful effect was increased (OR, 1.53; 95% CI, 1.14-2.05).
Among the 15 published randomized trials on the effects of convalescent plasma, no decreases in mortality were observed among patients treated with high-titer convalescent plasma (RR, 0.97; 95% CI, 0.92-1.02) or those treated with unselected convalescent plasma (RR, 1.25; 95% CI, 0.92-1.69).
This study was limited by its open-label design. The investigators noted that “additional randomized trials are warranted to assess the early use of high-titer convalescent plasma units in immunocompromised patients with COVID-19 who are unable to mount an efficient anti-SARS-CoV-2 antibody response.”
“The lack of benefit and the potential concern of harm caution against the unrestricted use of convalescent plasma for hospitalized patients with COVID-19,” the investigators concluded.
Bégin P, Callum J, Jamula E, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med. Published online September 9, 2021. doi:10.1038/s41591-021-01488-2