Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Abstract

Background: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point 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.

Results: A total of 160 patients underwent randomization. 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.

Conclusions: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

Figure 1. Time to the Development of Severe Respiratory Disease Due to Coronavirus Disease 2019, According to Trial Group in the Intention-to-Treat Analysis.

Shown are Kaplan–Meier estimates of the time from the intervention (administration of convalescent plasma or placebo) to the development of severe respiratory disease. The tick marks on the curves represent the interquartile range in the Kaplan–Meier time-to-event analysis in the convalescent plasma and placebo groups.

Figure 2. SARS-CoV-2 Serum Titers, According to Trial Group.

Shown are IgG antibody titers against SARS-CoV-2 spike (S) protein in the convalescent plasma and placebo groups 24 hours after infusion. The horizontal bars indicate medians, and the shaded gray areas interquartile ranges. Each circle represents one patient.