Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study

• Published in: BMC infectious diseases 2022-06, Vol.22 (1), p.1-575, Article 575
• Main Authors: Rojas, Manuel, Rodríguez, Yhojan, Hernández, Juan Carlos, Díaz-Coronado, Juan C, Vergara, José Alejandro Daza, Vélez, Verónica Posada, Mancilla, Jessica Porras, Araujo, Iván, Yepes, Jairo Torres, Ricaurte, Oscar Briceéo, Pardo-Oviedo, Juan Mauricio, Monsalve, Diana M, Acosta-Ampudia, Yeny, Ramírez-Santana, Carolina, García, Paula Gaviria, Landinez, Lina Acevedo, Correales, Luisa Duarte, Grass, Jeser Santiago, Pérez, Cristian Ricaurte, López, Gustavo Salguero, Mateus, Nataly, Mancera, Laura, Devia, Ronald Rengifo, Orjuela, Juan Esteban, Parra-Moreno, Christian R, Buitrago, Andrés Alfonso, Ordoéez, Inés Elvira, Osorio, Claudia Fabra, Ballesteros, Nathalia, Patiéo, Luz H, Castaéeda, Sergio, Muéoz, Marina, Ramírez, Juan David, Bastard, Paul, Gervais, Adrian, Bizien, Lucy, Casanova, Jean-Laurent, Camacho, Bernardo, Gallo, Juan Esteban, Gómez, Oscar, Rojas-Villarraga, Adriana, Pérez, Carlos E, Manrique, Rubén, Mantilla, Rubén D, Anaya, Juan-Manuel
• Format: Article
• Language: English
• Subjects: Antibodies; Bioinformatics; Clinical outcomes; Clinical trial; Clinical trials; Convalescent plasma; Coronaviruses; COVID-19; Disease; Disease control; Immunoglobulin A; Immunoglobulin G; Infections; Infectious diseases; Informed consent; Interferon; Laboratories; Mechanical ventilation; Mortality; Pandemics; Patients; Plasma; Pregnancy; Safety; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Testing; Transfusion; Ventilators; Viral antibodies; Viral diseases; Viral infections
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-022-07560-7

Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG [greater than or equai to] 1:3200 and IgA [greater than or equai to] 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay.