Early high-titer plasma therapy to prevent severe Covid-19 in older adults

LIBSTER, R.; MARC, G. PÉREZ; WAPPNER, D.; COVIELLO, S.; BIANCHI, A.; BRAEM, V.; ESTEBAN, I.; CABALLERO, M.T.; WOOD, C.; BERRUETA, M.; RONDAN, A.; LESCANO, G.; CRUZ, P.; RITOU, Y.; VIÑA, V. FERNÁNDEZ; PAGGI, D. ÁLVAREZ; ESPERANTE, S.; FERRETI, A.; OFMAN, G.; CIGANDA, Á.; RODRIGUEZ, R.; LANTOS, J.; VALENTINI, R.; ITCOVICI, N.; HINTZE, A.; OYARVIDE, M.L.; ETCHEGARAY, C.; NEIRA, A.; NAME, I.; ALFONSO, J.; CASTELO, R.; CARUSO, G.; RAPELIUS, S.; ALVEZ, F.; ETCHENIQUE, F.; DIMASE, F.; ALVAREZ, D.; ARANDA, S.S.; YANOTTI, C. SÁNCHEZ; DE LUCA, J.; BAGLIVO, S. JARES; LAUDANNO, S.; NOWOGRODZKI, F.; LARREA, R.; SILVEYRA, M.; LEBERZSTEIN, G.; DEBONIS, A.; MOLINOS, J.; GONZÁLEZ, M.; PEREZ, E.; KREPLAK, N.; ARGÜELLO, S. PASTOR; GIBBONS, L.; ALTHABE, F.; BERGEL, E.; POLACK, F.P.

NEW ENGLAND JOURNAL OF MEDICINE

MASSACHUSETTS MEDICAL SOC

Año: 2021 vol. 384 p. 610 - 618

0028-4793

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.).