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

Libster, R.; Perez Marc, G.; Wappner, D.; Coviello, S.; Bianchi, A.; Braem, V.; Esteban, I.; Caballero, M. T.; Wood, C. J.; Berrueta, M.; Rondan, A.; Lescano, G.; Cruz, P.; Ritou, I.; Fernandez Vina, V.; Alvarez Paggi, D.; Esperante, S.; Ferretti, A.; Ofman, G.; Ciganda, A.; Rodriguez, R.; Lantos, J.; Valentini, R.; Itcovici, N.; Hintze, A.; Oyarvide, L.; Etchegaray, C.; Neira, A.; Name, I.; Alfonso, J.; Lopez Castelo, R.; Caruso, G.; Rapelius, S.; Alvez, F.; Etchenique, F. C.; Dimase, F.; Alvarez, D. R.; Aranda, S. S.; Sanchez Yanotti, C.; DeLuca, J.; Jarez Baglivo, S.; Laudanno, S. L.; Nowog,

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 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), 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.