Abstract: (2022) 22:575 Rojas et al. BMC Infectious Diseases https://doi.org/10.1186/s12879-022-07560-7 Open Access RESEARCH Safety and efficacy of convalescent plasma for severe COVID‑19: a randomized, single blinded, parallel, controlled clinical study Manuel Rojas1,2, Yhojan Rodríguez3, Juan Carlos Hernández4, Juan C. Díaz‑Coronado5, José Alejandro Daza Vergara6, Verónica Posada Vélez7, Jessica Porras Mancilla7, Iván Araujo5, Jairo Torres Yepes6, Oscar Briceño Ricaurte6, Juan Mauricio Pardo‑Oviedo6, Diana M. Monsalve3, Yeny Acosta‑Ampudia3, Carolina Ramírez‑Santana3, Paula Gaviria García8, Lina Acevedo Landinez8, Luisa Duarte Correales8, Jeser Santiago Grass8, Cristian Ricaurte Pérez8, Gustavo Salguero López8, Nataly Mateus4, Laura Mancera4, Ronald Rengifo Devia4, Juan Esteban Orjuela4, Christian R. Parra‑Moreno4, Andrés Alfonso Buitrago4, Inés Elvira Ordoñez4, Claudia Fabra Osorio7, Nathalia Ballesteros9, Luz H. Patiño9, Sergio Castañeda9, Marina Muñoz9, Juan David Ramírez9,10, Paul Bastard11,12,13,14, Adrian Gervais13,15, Lucy Bizien13,15, Jean‑Laurent Casanova12,13,14,16,17,18, Bernardo Camacho8, Juan Esteban Gallo19, Oscar Gómez19, Adriana Rojas‑Villarraga20, Carlos E. Pérez21, Rubén Manrique22, Rubén D. Mantilla3 and Juan‑Manuel Anaya3,23* Abstract Background: 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. Methods: 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 ≥ 1:3200 and IgA ≥ 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. Results: 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 *Correspondence: anayajm@gmail.com 23 Present Address: LifeFactors, Rionegro, Colombia Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as..