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

Libster, Romina; Pérez Marc, Gonzalo; Wappner, Diego; Coviello, Silvina; Bianchi, Alejandra; Braem, Virginia; Esteban, Ignacio; Caballero, Mauricio T.; Wood, Cristian; Berrueta, Mabel; Rondan, Aníbal; Lescano, Gabriela; Cruz, Pablo; Ritou, Yvonne; Fernández Viña, Valeria; Álvarez Paggi, Damián; Esperante, Sebastián; Ferreti, Adrián; Ofman, Gastón; Ciganda, Álvaro; Rodriguez, Rocío; Lantos, Jorge; Valentini, Ricardo; Itcovici, Nicolás; Hintze, Alejandra; Oyarvide, M. Laura; Etchegaray, Candela; Neira, Alejandra; Name, Ivonne; Alfonso, Julieta; López Castelo, Rocío; Caruso, Gisela; Rapelius, Sofía; Alvez, Fernando; Etchenique, Federico; Dimase, Federico; Alvarez, Darío; Aranda, Sofía S.; Sánchez Yanotti, Clara; De Luca, Julián; Jares Baglivo, Sofía; Laudanno, Sofía; Nowogrodzki, Florencia; Larrea, Ramiro; Silveyra, María; Leberzstein, Gabriel; Debonis, Alejandra; Molinos, Juan; González, Miguel; Perez, Eduardo; Kreplak, Nicolás; Pastor Argüello, Susana; Gibbons, Luz; Althabe, Fernando; Bergel, Eduardo; Polack, Fernando P.

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.)