1. Prevention of severe COVID-19 in the elderly by early high-titer plasma
- Author
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Rocio Rodriguez, Mariano Girasolli, Viviana Dominguez, Valeria Fernandez Vina, Jorge Lantos, Florencia Nowogrodzki, Julian DeLuca, Sofia Lujan Laudanno, Clarisa Taffarel, Florencia Izetta, Maria del Carmen Nigro, Nicolás Kreplak, Fernando Alvez, Laura Oyarvide, Ivonne Ritou, Emmanuel Ezequiel Valls, Dario Raul Alvarez, Patricia Lesch, Indira Pichetto Olanda, Florencia De la Fuente, Camila Witteveen, Sebastian Esperante, Juan Rusconi, Sofia Sol Aranda, Juan Canela, Ricardo Valentini, Mauricio T. Caballero, Clara Sanchez Yanotti, Paula Fernandez Estrella, Gisela Caruso, Patricia Rearte Carvalho, Ramiro Manuel Larrea, Candela Etchegaray, Romina Libster, Cecilia Pampuro, Fernando P. Polack, Jose L Scapellato, Micaela Piani, Julieta Alfonso, Daniela Carolina Galnarez, Maria Eugenia Macaneo, Federico Dimase, Agustina Venditti, Juan Molinos, Cristina Soler Riera, Jimena Ochoa, Luz Gibbons, Eduardo Perez, Rocio Zarlenga, Alejandra Hintze, Guido Ochoa, Damian Alvarez Paggi, Silvina Kuperman, Virginia Braem, Mariano Aizpurua, Alfonso Raggio, Miguel Santiago Gonzalez, Maria Teresa Paniguetti, Maria Fernanda Caracciolo, Gabriela Lescano, Juan Mauricio Vargas, Silvina Coviello, Fernando Althabe, Sofia Jarez Baglivo, Juan Sebastian Riera, Anibal Rondan, Mario Rovere, Gaston Pellegrino, Nicolas Itcovici, Yanina Miragaya, Alejandra Neira, Carla Marchionatti, Silvana Marquez, Maria Emilia Gutierrez Meyer, Gonzalo Pérez Marc, Marcela Balduzzi, Lia Pocket, Mabel Berrueta, Romina Zadoff, Noelia Iraizos, Susana Villaroel, Eduardo Bergel, Rocio Lopez Castelo, Maria Veronica Paz, Maria Dolores Silveyra, Maximiliano de Zan, Agostina Pagella, Lucila DiNunzio, Jimena Franco, Romina Militerno, Natalia Garcia Escude, Gabriela Leberzstein, Diego Wappner, Pablo Cruz, Romina Romero, Jorge Geffner, Susana Pastor Arguello, Leonel Langellotti, Andrea V. Gamarnik, Alejandra Debonis, Ignacio Esteban, Gaston Ofman, Federico Cesar Etchenique, Cristian Wood, Ivonne Name, Natali Estrada, Sebastian Perez Marc, Enio Garcia, Sofia Rapelius, Alvaro Ciganda, Alejandra Bianchi, and Adrian Ferretti
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medicine.medical_specialty ,Randomization ,Respiratory rate ,business.industry ,Respiratory disease ,Placebo ,medicine.disease ,Titer ,Internal medicine ,Number needed to treat ,Clinical endpoint ,Medicine ,business ,Adverse effect - Abstract
BackgroundTherapies 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.MethodsA 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 O2satResults160 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.ConclusionsEarly 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.
- Published
- 2020
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