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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Date
2021-11-20Author
Axfors, Cathrine
Janiaud, Perrine
Schmitt, Andreas M.
van’t Hooft, Janneke
Smith, Emily R.
Haber, Noah A.
Abayomi, Akin
Abduljalil, Manal
Abdulrahman, Abdulkarim
Acosta-Ampudia, Yeny
Aguilar-Guisado, Manuela
Al-Beidh, Farah
Alejandria, Marissa M.
Alfonso, Rachelle N.
Ali, Mohammad
AlQahtani, Manaf
AlZamrooni, Alaa
Anaya, Juan-Manuel
Ang, Mark A. C.
Aomar, Ismael F.
Argumanis, Luis E.
Averyanov, Alexander
Baklaushev, Vladimir P.
Balionis, Olga
Benfield, Thomas
Berry, Scott
Birocco, Nadia
Bonifacio, Lynn B.
Bowen, Asha C.
Bown, Abbie
Cabello-Gutierrez, Carlos
Camacho, Bernardo
Camacho-Ortiz, Adrian
Campbell-Lee, Sally
Cao, Damon H.
Cardesa, Ana
Carnate, Jose M.
Castillo, German J. J.
Cavallo, Rossana
Chowdhury, Fazle R.
Chowdhury, Forhad U. H.
Ciccone, Giovannino
Cingolani, Antonella
Climacosa, Fresthel M. M.
Compernolle, Veerle
Cortez, Carlo F. N.
Costa Neto, Abel
D’Antico, Sergio
Daly, James
Danielle, Franca
Davis, Joshua S.
De Rosa, Francesco G.
Denholm, Justin T.
Denkinger, Claudia M.
Desmecht, Daniel
Díaz-Coronado, Juan C.
Díaz Ponce-Medrano, Juan A.
Donneau, Anne-Françoise
Dumagay, Teresita E.
Dunachie, Susanna
Dungog, Cecile C.
Erinoso, Olufemi
Escasa, Ivy M. S.
Estcourt, Lise J.
Evans, Amy
Evasan, Agnes L. M.
Fareli, Christian J.
Fernandez-Sanchez, Veronica
Galassi, Claudia
Gallo, Juan E.
Garcia, Patricia J.
Garcia, Patricia L.
Garcia, Jesus A.
Garigliany, Mutien
Garza-Gonzalez, Elvira
Gauiran, Deonne T. V.
Gaviria García, Paula A.
Giron-Gonzalez, Jose-Antonio
Gómez-Almaguer, David
Gordon, Anthony C.
Gothot, André
Grass Guaqueta, Jeser S.
Green, Cameron
Grimaldi, David
Hammond, Naomi E.
Harvala, Heli
Heralde, Francisco M.
Herrick, Jesica
Higgins, Alisa M.
Hills, Thomas E.
Hines, Jennifer
Holm, Karin
Hoque, Ashraful
Hoste, Eric
Ignacio, Jose M.
Ivanov, Alexander V.
Janssen, Maike
Jennings, Jeffrey H.
Jha, Vivekanand
King, Ruby A. N.
Kjeldsen-Kragh, Jens
Klenerman, Paul
Kotecha, Aditya
Krapp, Fiorella
Labanca, Luciana
Laing, Emma
Landin-Olsson, Mona
Laterre, Pierre-François
Lim, Lyn-Li
Lim, Jodor
Ljungquist, Oskar
Llaca-Díaz, Jorge M.
López-Robles, Concepción
López-Cárdenas, Salvador
Lopez-Plaza, Ileana
Lucero, Josephine A. C.
Lundgren, Maria
Macías, Juan
Maganito, Sandy C.
Malundo, Anna F. G.
Manrique, Rubén D.
Manzini, Paola M.
Marcos, Miguel
Marquez, Ignacio
Martínez-Marcos, Francisco J.
Mata, Ana M.
McArthur, Colin J.
McQuilten, Zoe K.
McVerry, Bryan J.
Menon, David K.
Meyfroidt, Geert
Mirasol, Ma. A. L.
Misset, Benoît
Molton, James S.
Mondragon, Alric V.
Monsalve, Diana M.
Moradi Choghakabodi, Parastoo
Morpeth, Susan C.
Mouncey, Paul R.
Moutschen, Michel
Müller-Tidow, Carsten
Murphy, Erin
Najdovski, Tome
Nichol, Alistair D.
Nielsen, Henrik
Novak, Richard M.
O’Sullivan, Matthew V. N.
Olalla, Julian
Osibogun, Akin
Osikomaiya, Bodunrin
Oyonarte, Salvador
Pardo-Oviedo, Juan M.
Patel, Mahesh C.
Paterson, David L.
Peña-Perez, Carlos A.
Perez-Calatayud, Angel A.
Pérez-Alba, Eduardo
Perkina, Anastasia
Perry, Naomi
Pouladzadeh, Mandana
Poyato, Inmaculada
Price, David J.
Quero, Anne K. H.
Rahman, Md. M.
Rahman, Md. S.
Ramesh, Mayur
Ramírez-Santana, Carolina
Rasmussen, Magnus
Rees, Megan A.
Rego, Eduardo
Roberts, Jason A.
Roberts, David J.
Rodríguez, Yhojan
Rodríguez-Baño, Jesús
Rogers, Benjamin A.
Rojas, Manuel
Romero, Alberto
Rowan, Kathryn M.
Saccona, Fabio
Safdarian, Mehdi
Santos, Maria C. M.
Sasadeusz, Joe
Scozzari, Gitana
Shankar-Hari, Manu
Sharma, Gorav
Snelling, Thomas
Soto, Alonso
Tagayuna, Pedrito Y.
Tang, Amy
Tatem, Geneva
Teofili, Luciana
Tong, Steven Y. C.
Turgeon, Alexis F.
Veloso, Januario D.
Venkatesh, Balasubramanian
Ventura-Enriquez, Yanet
Webb, Steve A.
Wiese, Lothar
Wikén, Christian
Wood, Erica M.
Yusubalieva, Gaukhar M.
Zacharowski, Kai
Zarychanski, Ryan
Khanna, Nina
Moher, David
Goodman, Steven N.
Ioannidis, John P. A.
Hemkens, Lars G.
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Show full item recordAbstract
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.
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