Prevention of severe COVID-19 in the elderly by early high-titer plasma therapy

By R. Libster, G. P. Marc, Diego Wappner, Silvina Coviello, Alejandra M Bianchi, Virginia Braem, I. Esteban, M. Caballero, Cristian Wood, M. Berrueta and 46 more. New England Journal of Medicine, 2021

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Background Therapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression. Methods A randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV-2 in elderly subjects within 72 hours of the beginning of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible. Results 160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%. A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81)]. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed. Conclusions Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected seniors reduced COVID-19 progression. This safe, outpatient intervention facilitates access to treatment from industrialized to low and middle-income countries (LMIC), can decompress demands on hospitals, and may contribute to save lives. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163).

Subfields: General Health Professions, Infectious Diseases

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