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01-12-2021 | Severe Acute Respiratory Syndrome Coronavirus | Research article

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

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

Published in: BMC Infectious Diseases | Issue 1/2021

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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Title: Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials
Authors: Cathrine Axfors
Perrine Janiaud
Andreas M. Schmitt
Janneke van’t Hooft
Emily R. Smith
Noah A. 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 AlZamrooni
Juan-Manuel Anaya
Mark Angelo C. Ang
Ismael F. Aomar
Luis E. Argumanis
Alexander Averyanov
Vladimir P. Baklaushev
Olga Balionis
Thomas Benfield
Scott Berry
Nadia Birocco
Lynn B. Bonifacio
Asha C. Bowen
Abbie Bown
Carlos Cabello-Gutierrez
Bernardo Camacho
Adrian Camacho-Ortiz
Sally Campbell-Lee
Damon H. Cao
Ana Cardesa
Jose M. Carnate
German Jr. J. Castillo
Rossana Cavallo
Fazle R. Chowdhury
Forhad U. H. 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
Daniel Desmecht
Juan C. Díaz-Coronado
Juan A. Díaz Ponce-Medrano
Anne-Françoise Donneau
Teresita E. Dumagay
Susanna Dunachie
Cecile C. Dungog
Olufemi Erinoso
Ivy Mae S. Escasa
Lise J. Estcourt
Amy Evans
Agnes L. M. Evasan
Christian J. Fareli
Veronica Fernandez-Sanchez
Claudia Galassi
Juan E. Gallo
Patricia J. Garcia
Patricia L. Garcia
Jesus A. Garcia
Mutien Garigliany
Elvira Garza-Gonzalez
Deonne Thaddeus V. Gauiran
Paula A. Gaviria García
Jose-Antonio Giron-Gonzalez
David Gómez-Almaguer
Anthony C. Gordon
André Gothot
Jeser Santiago Grass Guaqueta
Cameron Green
David Grimaldi
Naomi E. Hammond
Heli Harvala
Francisco M. Heralde
Jesica Herrick
Alisa M. Higgins
Thomas E. Hills
Jennifer Hines
Karin Holm
Ashraful Hoque
Eric Hoste
Jose M. Ignacio
Alexander V. Ivanov
Maike Janssen
Jeffrey H. Jennings
Vivekanand Jha
Ruby Anne N. King
Jens Kjeldsen-Kragh
Paul Klenerman
Aditya Kotecha
Fiorella Krapp
Luciana Labanca
Emma Laing
Mona Landin-Olsson
Pierre-François Laterre
Lyn-Li Lim
Jodor Lim
Oskar Ljungquist
Jorge M. Llaca-Díaz
Concepción López-Robles
Salvador López-Cárdenas
Ileana Lopez-Plaza
Josephine Anne C. Lucero
Maria Lundgren
Juan Macías
Sandy C. Maganito
Anna Flor G. Malundo
Rubén D. Manrique
Paola M. Manzini
Miguel Marcos
Ignacio Marquez
Francisco Javier Martínez-Marcos
Ana M. Mata
Colin J. McArthur
Zoe K. McQuilten
Bryan J. McVerry
David K. Menon
Geert Meyfroidt
Ma. Angelina L. Mirasol
Benoît Misset
James S. Molton
Alric V. Mondragon
Diana M. Monsalve
Parastoo Moradi Choghakabodi
Susan C. Morpeth
Paul R. Mouncey
Michel Moutschen
Carsten Müller-Tidow
Erin Murphy
Tome Najdovski
Alistair D. Nichol
Henrik Nielsen
Richard M. Novak
Matthew V. N. O’Sullivan
Julian Olalla
Akin Osibogun
Bodunrin Osikomaiya
Salvador Oyonarte
Juan M. Pardo-Oviedo
Mahesh C. Patel
David L. Paterson
Carlos A. Peña-Perez
Angel A. Perez-Calatayud
Eduardo Pérez-Alba
Anastasia Perkina
Naomi Perry
Mandana Pouladzadeh
Inmaculada Poyato
David J. Price
Anne Kristine H. Quero
Md. M. Rahman
Md. S. Rahman
Mayur Ramesh
Carolina Ramírez-Santana
Magnus Rasmussen
Megan A. Rees
Eduardo Rego
Jason A. Roberts
David J. Roberts
Yhojan Rodríguez
Jesús Rodríguez-Baño
Benjamin A. Rogers
Manuel Rojas
Alberto Romero
Kathryn M. Rowan
Fabio Saccona
Mehdi Safdarian
Maria Clariza M. Santos
Joe Sasadeusz
Gitana Scozzari
Manu Shankar-Hari
Gorav Sharma
Thomas Snelling
Alonso Soto
Pedrito Y. Tagayuna
Amy Tang
Geneva Tatem
Luciana Teofili
Steven Y. C. Tong
Alexis F. Turgeon
Januario D. Veloso
Balasubramanian Venkatesh
Yanet Ventura-Enriquez
Steve A. Webb
Lothar Wiese
Christian Wikén
Erica M. Wood
Gaukhar M. Yusubalieva
Kai Zacharowski
Ryan Zarychanski
Nina Khanna
David Moher
Steven N. Goodman
John P. A. Ioannidis
Lars G. Hemkens
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Severe Acute Respiratory Syndrome Coronavirus
COVID-19
Published in: BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-021-06829-7

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

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Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

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The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

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Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

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Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

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Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

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New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

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Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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