Prevention of severe COVID-19 in the elderly by early high-titer plasma
Authors: Libster Romina , Marc Gonzalo Pérez , 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 , Viña Valeria Fernández , Paggi Damián Álvarez , Esperante Sebastián , Ferreti Adrián , Ofman Gastón , Ciganda Álvaro , Rodriguez Rocío , Lantos Jorge , Valentini Ricardo , Itcovici Nicolás , Hintze Alejandra , Oyarvide María Laura , Etchegaray Candela , Neira Alejandra , Name Ivonne , Alfonso Julieta , Castelo Rocío López , Caruso Gisela , Rapelius Sofía , Alvez Fernando , Etchenique Federico , Dimase Federico , Alvarez Darío , Aranda Sofía , Yanotti Clara Sánchez , De Luca Julián , Baviglio Sofía Jares , Laudanno Sofía , Nowogrodzki Florencia , Larrea Ramiro , Silveyra María , Leberzstein Gabriel , Debonis Alejandra , Molinos Juan , González Miguel , Perez Eduardo , Kreplak Nicolás , Argüello Susana Pastor , Gibbons Luz , Althabe Fernando , Bergel Eduardo , Polack Fernando P. ,   for the Fundación INFANT-COVID-19 Group
Published: November 2020

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-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2sat<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), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed.

Conclusions

Early administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives.

Funded by The Bill & Melinda Gates Foundation and The Fundación INFANT Pandemic Fund. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163).

All authors have completed the ICMJE uniform disclosure form atwww.icmje.org/coi_disclosure.pdfand declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.