Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials
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BioMed Central Ltd
Axfors, C., Janiaud, P., Schmitt, A.M. et al. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials. BMC Infect Dis 21, 1170 (2021). [https://doi.org/10.1186/s12879-021-06829-7]
SponsorshipAmalia Bravo-Lindoro; BHP Foundation; Blanceflor Foundation; Department of Foreign Affairs, Trade, and Development of Canada; Eli Omar Zavaleta; Erik and Susanna Olesen’s Charitable Fund; Federal Ministry of Education and Research in Germany; Fundación Telefónica del Perú; IDCBIS; ISA Group and Suramericana; Kai Hansen Foundation; Katja Suter and Sina Ullrich; Khuzestan Blood Transfusion Organization; Macquarie Group Foundation; Medical Research Future Fund; NephroPlus; RBWH; Roel Rolando-Almario NCT04385199; Royal Brisbane; Sheri Renaud; Simonsen Foundation; UKRI-National Institute for Health Research UK; UKRIDHSC COV19-RECPLAS; UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009; Women’s Hospital Foundation; National Institutes of Health; National Heart, Lung, and Blood Institute; Pittsburgh Foundation; Pfizer; Baxter International; Stanford University; Gilead Sciences; National Institute on Handicapped Research RP-2015-06-18; Meso Scale Diagnostics; Universität Basel; Laura and John Arnold Foundation; Health Research Board; Pratt Foundation; Canadian Institutes of Health Research; National Institute for Health Research; Department of Health and Social Care; European Commission 101015756; National Health and Medical Research Council; Department of Science and Technology, Ministry of Science and Technology, India; Health Research Council of New Zealand; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; Sweden-America Foundation; Bundesministerium für Bildung und Forschung; Lundbeckfonden; Knut och Alice Wallenbergs Stiftelse; Seventh Framework Programme; Ahvaz Jundishapur University of Medical Sciences; Université Pierre et Marie Curie; Uppsala Universitet; Horizon 2020; Svenska Läkaresällskapet; Universidad del Rosario; Pharmaceuticals Bayer; Novo Nordisk Fonden; Department of Science and Technology, Philippines; Philippine Council for Health Research and Development; Minderoo Foundation
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 (I2 = 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.