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and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ).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 Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.

RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients).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 The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.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.


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 you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Cite as

Axfors, C., Janiaud, P., Schmitt, A., Van't Hooft, J., Smith, E., Haber, N., Abayomi, A., Abduljalil, M., Abdulrahman, A., Acosta-Ampudia, Y., Aguilar-Guisado, M., Al-Beidh, F., Alejandria, M., Alfonso, R., Ali, M., AlQahtani, M., AlZamrooni, A., Anaya, J., Ang, M., Aomar, I., Argumanis, L., Averyanov, A., Baklaushev, V., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L., Bowen, A., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D., Cardesa, A., Carnate, J., Castillo, G., Cavallo, R., Chowdhury, F., Chowdhury, F., Ciccone, G., Cingolani, A., Climacosa, F., Compernolle, V., Cortez, C., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J., De Rosa, F., Denholm, J., Denkinger, C., Desmecht, D., Díaz-Coronado, J., Díaz Ponce-Medrano, J., Donneau, A., Dumagay, T., Dunachie, S., Dungog, C., Erinoso, O., Escasa, I., Estcourt, L., Evans, A., Evasan, A., Fareli, C., Fernandez-Sanchez, V., Galassi, C., Gallo, J., Garcia, P., Garcia, P., Garcia, J., Garigliany, M., Garza-Gonzalez, E., Gauiran, D., Gaviria García, P., Giron-Gonzalez, J., Gómez-Almaguer, D., Gordon, A., Gothot, A., Grass Guaqueta, J., Green, C., Grimaldi, D., Hammond, N., Harvala, H., Heralde, F., Herrick, J., Higgins, A., Hills, T., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J., Ivanov, A., Janssen, M., Jennings, J., Jha, V., King, R., Kjeldsen-Kragh, J., Klenerman, P., Kotecha, A., Krapp, F., Labanca, L., Laing, E., Landin-Olsson, M., Laterre, P., Lim, L., Lim, J., Ljungquist, O., Llaca-Díaz, J., López-Robles, C., López-Cárdenas, S., Lopez-Plaza, I., Lucero, J., Lundgren, M., Macías, J., Maganito, S., Malundo, A., Manrique, R., Manzini, P., Marcos, M., Marquez, I., Martínez-Marcos, F., Mata, A., McArthur, C., McQuilten, Z., McVerry, B., Menon, D., Meyfroidt, G., Mirasol, M., Misset, B., Molton, J., Mondragon, A., Monsalve, D., Moradi Choghakabodi, P., Morpeth, S., Mouncey, P., Moutschen, M., Müller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A., Nielsen, H., Novak, R., O'Sullivan, M., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J., Patel, M., Paterson, D., Peña-Perez, C., Perez-Calatayud, A., Pérez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D., Quero, A., Rahman, M., Rahman, M., Ramesh, M., Ramírez-Santana, C., Rasmussen, M., Rees, M., Rego, E., Roberts, J., Roberts, D., Rodríguez, Y., Rodríguez-Baño, J., Rogers, B., Rojas, M., Romero, A., Rowan, K., Saccona, F., Safdarian, M., Santos, M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P., Tang, A., Tatem, G., Teofili, L., Tong, S., Turgeon, A., Veloso, J., Venkatesh, B., Ventura-Enriquez, Y., Webb, S., Wiese, L., Wikén, C., Wood, E., Yusubalieva, G., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S., Ioannidis, J. & Hemkens, L. 2021, 'Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials', BMC Infectious Diseases, 21, article no: 1170. https://doi.org/10.1186/s12879-021-06829-7

Downloadable citations

Download HTML citationHTML Download BIB citationBIB Download RIS citationRIS
Last updated: 16 June 2022
Was this page helpful?