tetano
Editor, Senior Moderator
N Engl J Med
. 2021 Jan 6.
doi: 10.1056/NEJMoa2033700. Online ahead of print.
Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults
Romina Libster[SUP] 1 [/SUP], Gonzalo P?rez Marc[SUP] 1 [/SUP], Diego Wappner[SUP] 1 [/SUP], Silvina Coviello[SUP] 1 [/SUP], Alejandra Bianchi[SUP] 1 [/SUP], Virginia Braem[SUP] 1 [/SUP], Ignacio Esteban[SUP] 1 [/SUP], Mauricio T Caballero[SUP] 1 [/SUP], Cristian Wood[SUP] 1 [/SUP], Mabel Berrueta[SUP] 1 [/SUP], An?bal Rondan[SUP] 1 [/SUP], Gabriela Lescano[SUP] 1 [/SUP], Pablo Cruz[SUP] 1 [/SUP], Yvonne Ritou[SUP] 1 [/SUP], Valeria Fern?ndez Vi?a[SUP] 1 [/SUP], Dami?n ?lvarez Paggi[SUP] 1 [/SUP], Sebasti?n Esperante[SUP] 1 [/SUP], Adri?n Ferreti[SUP] 1 [/SUP], Gast?n Ofman[SUP] 1 [/SUP], ?lvaro Ciganda[SUP] 1 [/SUP], Roc?o Rodriguez[SUP] 1 [/SUP], Jorge Lantos[SUP] 1 [/SUP], Ricardo Valentini[SUP] 1 [/SUP], Nicol?s Itcovici[SUP] 1 [/SUP], Alejandra Hintze[SUP] 1 [/SUP], M Laura Oyarvide[SUP] 1 [/SUP], Candela Etchegaray[SUP] 1 [/SUP], Alejandra Neira[SUP] 1 [/SUP], Ivonne Name[SUP] 1 [/SUP], Julieta Alfonso[SUP] 1 [/SUP], Roc?o L?pez Castelo[SUP] 1 [/SUP], Gisela Caruso[SUP] 1 [/SUP], Sof?a Rapelius[SUP] 1 [/SUP], Fernando Alvez[SUP] 1 [/SUP], Federico Etchenique[SUP] 1 [/SUP], Federico Dimase[SUP] 1 [/SUP], Dar?o Alvarez[SUP] 1 [/SUP], Sof?a S Aranda[SUP] 1 [/SUP], Clara S?nchez Yanotti[SUP] 1 [/SUP], Juli?n De Luca[SUP] 1 [/SUP], Sof?a Jares Baglivo[SUP] 1 [/SUP], Sof?a Laudanno[SUP] 1 [/SUP], Florencia Nowogrodzki[SUP] 1 [/SUP], Ramiro Larrea[SUP] 1 [/SUP], Mar?a Silveyra[SUP] 1 [/SUP], Gabriel Leberzstein[SUP] 1 [/SUP], Alejandra Debonis[SUP] 1 [/SUP], Juan Molinos[SUP] 1 [/SUP], Miguel Gonz?lez[SUP] 1 [/SUP], Eduardo Perez[SUP] 1 [/SUP], Nicol?s Kreplak[SUP] 1 [/SUP], Susana Pastor Arg?ello[SUP] 1 [/SUP], Luz Gibbons[SUP] 1 [/SUP], Fernando Althabe[SUP] 1 [/SUP], Eduardo Bergel[SUP] 1 [/SUP], Fernando P Polack[SUP] 1 [/SUP], Fundaci?n INFANT–COVID-19 Group
Affiliations
Abstract
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 Fundaci?n INFANT Pandemic Fund; Direcci?n 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.).
. 2021 Jan 6.
doi: 10.1056/NEJMoa2033700. Online ahead of print.
Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults
Romina Libster[SUP] 1 [/SUP], Gonzalo P?rez Marc[SUP] 1 [/SUP], Diego Wappner[SUP] 1 [/SUP], Silvina Coviello[SUP] 1 [/SUP], Alejandra Bianchi[SUP] 1 [/SUP], Virginia Braem[SUP] 1 [/SUP], Ignacio Esteban[SUP] 1 [/SUP], Mauricio T Caballero[SUP] 1 [/SUP], Cristian Wood[SUP] 1 [/SUP], Mabel Berrueta[SUP] 1 [/SUP], An?bal Rondan[SUP] 1 [/SUP], Gabriela Lescano[SUP] 1 [/SUP], Pablo Cruz[SUP] 1 [/SUP], Yvonne Ritou[SUP] 1 [/SUP], Valeria Fern?ndez Vi?a[SUP] 1 [/SUP], Dami?n ?lvarez Paggi[SUP] 1 [/SUP], Sebasti?n Esperante[SUP] 1 [/SUP], Adri?n Ferreti[SUP] 1 [/SUP], Gast?n Ofman[SUP] 1 [/SUP], ?lvaro Ciganda[SUP] 1 [/SUP], Roc?o Rodriguez[SUP] 1 [/SUP], Jorge Lantos[SUP] 1 [/SUP], Ricardo Valentini[SUP] 1 [/SUP], Nicol?s Itcovici[SUP] 1 [/SUP], Alejandra Hintze[SUP] 1 [/SUP], M Laura Oyarvide[SUP] 1 [/SUP], Candela Etchegaray[SUP] 1 [/SUP], Alejandra Neira[SUP] 1 [/SUP], Ivonne Name[SUP] 1 [/SUP], Julieta Alfonso[SUP] 1 [/SUP], Roc?o L?pez Castelo[SUP] 1 [/SUP], Gisela Caruso[SUP] 1 [/SUP], Sof?a Rapelius[SUP] 1 [/SUP], Fernando Alvez[SUP] 1 [/SUP], Federico Etchenique[SUP] 1 [/SUP], Federico Dimase[SUP] 1 [/SUP], Dar?o Alvarez[SUP] 1 [/SUP], Sof?a S Aranda[SUP] 1 [/SUP], Clara S?nchez Yanotti[SUP] 1 [/SUP], Juli?n De Luca[SUP] 1 [/SUP], Sof?a Jares Baglivo[SUP] 1 [/SUP], Sof?a Laudanno[SUP] 1 [/SUP], Florencia Nowogrodzki[SUP] 1 [/SUP], Ramiro Larrea[SUP] 1 [/SUP], Mar?a Silveyra[SUP] 1 [/SUP], Gabriel Leberzstein[SUP] 1 [/SUP], Alejandra Debonis[SUP] 1 [/SUP], Juan Molinos[SUP] 1 [/SUP], Miguel Gonz?lez[SUP] 1 [/SUP], Eduardo Perez[SUP] 1 [/SUP], Nicol?s Kreplak[SUP] 1 [/SUP], Susana Pastor Arg?ello[SUP] 1 [/SUP], Luz Gibbons[SUP] 1 [/SUP], Fernando Althabe[SUP] 1 [/SUP], Eduardo Bergel[SUP] 1 [/SUP], Fernando P Polack[SUP] 1 [/SUP], Fundaci?n INFANT–COVID-19 Group
Affiliations
- PMID: 33406353
- DOI: 10.1056/NEJMoa2033700
Abstract
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 Fundaci?n INFANT Pandemic Fund; Direcci?n 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.).