Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials
Cathrine Axfors, Perrine Janiaud, Andreas M. Schmitt, Janneke van ’t Hooft, Emily R. Smith, Noah Haber, Akin Abayomi, Manal Abduljalil, Abdulkarim Abdulrahman, Yeny Acosta‐Ampudia, Manuela Aguilar‐Guisado, Farah Al-Beidh, Marissa M. Alejandria, Rachelle N. Alfonso, Mohammad Ali, Manaf AlQahtani, Alaa M Alzamrooni, Juan‐Manuel Anaya, Mark Angelo C. Ang, Ismael F. Aomar, Luis E. Argumanis, Alexander Averyanov, Владимир П. Баклаушев, Olga Balionis, Thomas Benfield, Scott Berry, Nadia Birocco, Lynn Bonifacio, Asha C Bowen, Abbie Bown, Carlos Cabello-Gutiérrez, Bernardo Camacho, Adrián Camacho-Ortíz, Sally A. Campbell‐Lee, Damon H. Cao, Ana Cardesa, Jose M. Carnate, German Jr. J. Castillo, Rossana Cavallo, Fazle Rabbi Chowdhury, Forhad Uddin Hasan Chowdhury, Giovannino Ciccone, Antonella Cingolani, Fresthel Monica M. Climacosa, Veerle Compernolle, Carlo Francisco N. Cortez, Abel Costa Neto, Sergio D’Antico, James Daly, Franca Danielle, Joshua S. Davis, Francesco Giuseppe De Rosa, Justin T. Denholm, Claudia M. Denkinger, Daniël Desmecht, Juan Camilo Díaz-Coronado, Juan Alberto Díaz Ponce-Medrano, Anne‐Françoise Donneau, Teresita Dumagay, Susanna Dunachie, Cecile C. Dungog, Olufemi Erinoso, Ivy Mae S. Escasa, Lise J Estcourt, Amy Evans, Agnes Lorrainne M. Evasan, Christian J. Fareli, Verónica Fernández-Sánchez, Claudia Galassi, Juan Esteban Gallo, Patricia García, Patricia L. García, Jesus Antonio Chávez García, Mutien‐Marie Garigliany, Elvira Garza‐González, Deonne Thaddeus V. Gauiran, Paula Andrea Gaviria García, J.A. Girón González, David Gómez‐Almaguer, Anthony Gordon, André Gothot, Jeser Santiago Grass Guaqueta, Cameron Green, David Grimaldi, Naomi Hammond, Heli Harvala, Francisco M. Heralde, Jesica A. Herrick, Alisa M. Higgins, Thomas Hills, Jennifer Hines, Karin Holm, Ashraful Hoque, Eric A. J. Hoste, José María Ignacio García, Alexander Vladimirovich Ivanov, Maike Janssen, Jeffrey Jennings, Vivekanand Jha, Ruby Anne King
Abstract
Abstract Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I 2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.