In patients with severe coronavirus disease 2019 (COVID-19) pneumonia, convalescent plasma did not result in significant clinical benefit or improvement in overall mortality compared to placebo, according to data published in the New England Journal of Medicine.
In this randomized, double-blind, placebo-controlled, multicenter trial (PlasmAr; ClinicalTrials.gov, NCT04383535), adult patients with severe COVID-19 pneumonia received either convalescent plasma or placebo in a 2:1 ratio. The primary outcome was patient’s clinical status 30 days after intervention, measured on a 6-point ordinal scale ranging from total recovery to death.
The study include 228 patients to receive convalescent plasma and 105 patients to receive placebo. At baseline, the median age was 62 years, 67.6% were men, and 64.9% had a coexisting condition upon enrollment. The total immunoglobulin G antibody median value was 1:3200. The median volume of convalescent plasma received by patients was 500 mL.
By day 30, investigators observed no significant differences between groups in the distribution of clinical outcomes (odds ratio [OR], 0.83; 95% CI, 0.52-1.35; P =.46), even after adjusting for sex, history of chronic obstructive pulmonary disease, and history of tobacco use (P = .70). Mortality at day 30 was 11.43% (12/105) in the placebo group and 10.96% (25/228) in the plasma group (risk difference, -0.46; 95% CI, -7.8 to 6.8).
Total SARS-CoV-2 antibody titers were identical at baseline, but by day 2, patients receiving plasma had higher levels than those receiving placebo. No differences in titers were observed by days 7 or 14. While infusion related adverse events were slightly higher in the plasma group compared to placebo, no significant differences were found in the overall incidence of adverse or serious adverse events.
A main limitation of the study was lack of standardized therapy in both groups.
“[T]he use of convalescent plasma therapy in addition to standard treatment in patients with severe pneumonia due to COVID-19 did not reduce mortality or improve other clinical outcomes at day 30 compared to placebo,” investigators concluded. They recommend re-evaluating the use of convalescent plasma as a standard of care in these patients.
Simonovich VA, Burgos Pratx LD, Scibona P, et al; for the PlasmAr Study Group. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. New Engl J Med. Published online November 24, 2020. doi:10.1056/NEJMoa2031304.