Randomised double-blinded placebo-controlled trial (Orange)
Therapies to interrupt the progression of early COVID-19 remain elusive. Among them, convalescent plasma administered to hospitalised patients has been unsuccessful to date, perhaps because antibodies should be administered earlier in the course of illness. In this article, the authors report the results of a randomised, double-blind, placebo-controlled trial of convalescent plasma with high IgG titres against SARS-CoV-2 in older adult patients within 72 hours after the onset of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of COVID-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.
Concerning the results, a total of 160 patients underwent randomisation. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. The authors concluded that early administration of high-titre convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of COVID-19.