Title
Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials
Date Issued
01 December 2021
Access level
open access
Resource Type
journal article
Author(s)
Axfors C.
Janiaud P.
Schmitt A.M.
van’t Hooft J.
Smith E.R.
Haber N.A.
Abayomi A.
Abduljalil M.
Abdulrahman A.
Acosta-Ampudia Y.
Aguilar-Guisado M.
Al-Beidh F.
Alejandria M.M.
Alfonso R.N.
Ali M.
AlQahtani M.
AlZamrooni A.
Anaya J.M.
Ang M.A.C.
Aomar I.F.
Argumanis L.E.
Averyanov A.
Baklaushev V.P.
Balionis O.
Benfield T.
Berry S.
Birocco N.
Bonifacio L.B.
Bowen A.C.
Bown A.
Cabello-Gutierrez C.
Camacho B.
Camacho-Ortiz A.
Campbell-Lee S.
Cao D.H.
Cardesa A.
Carnate J.M.
Castillo G.J.J.
Cavallo R.
Chowdhury F.R.
Chowdhury F.U.H.
Ciccone G.
Cingolani A.
Climacosa F.M.M.
Compernolle V.
Cortez C.F.N.
Costa Neto A.
D’Antico S.
Daly J.
Danielle F.
Davis J.S.
De Rosa F.G.
Denholm J.T.
Denkinger C.M.
Desmecht D.
Díaz-Coronado J.C.
Díaz Ponce-Medrano J.A.
Donneau A.F.
Dumagay T.E.
Dunachie S.
Dungog C.C.
Erinoso O.
Escasa I.M.S.
Estcourt L.J.
Evans A.
Evasan A.L.M.
Fareli C.J.
Fernandez-Sanchez V.
Galassi C.
Gallo J.E.
Garcia P.L.
Garcia J.A.
Garigliany M.
Garza-Gonzalez E.
Gauiran D.T.V.
Gaviria García P.A.
Giron-Gonzalez J.A.
Gómez-Almaguer D.
Gordon A.C.
Gothot A.
Grass Guaqueta J.S.
Green C.
Grimaldi D.
Hammond N.E.
Harvala H.
Heralde F.M.
Herrick J.
Higgins A.M.
Hills T.E.
Hines J.
Holm K.
Hoque A.
Hoste E.
Ignacio J.M.
Ivanov A.V.
Janssen M.
Jennings J.H.
Jha V.
King R.A.N.
Publisher(s)
BioMed Central Ltd
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and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX).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 (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.
Volume
21
Issue
1
Language
English
OCDE Knowledge area
Epidemiología
Subjects
Scopus EID
2-s2.0-85119521567
PubMed ID
Source
BMC Infectious Diseases
ISSN of the container
14712334
Sponsor(s)
This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing.
We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ra?l Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Su?rez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsg?rd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, C?cilie Leding, MD, Katrine Iversen, MD, Maria Engel M?ller, MD, H?kon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology?Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O?Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/).
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