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

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

doi:10.1186/s12879-021-06829-7

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

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 AomarLuis 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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Journal	BMC Infectious Diseases
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12879-021-06829-7
Publication status	Published - 20 Nov 2021

Keywords / Materials (for Non-textual outputs)

COVID-19/therapy
Humans
Immunization
Passive
Randomized Controlled Trials as Topic
SARS-CoV-2
Treatment Outcome

Access to Document

10.1186/s12879-021-06829-7

s12879-021-06829-7
© The Author(s) 2021. Open Access 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.
Final published version, 1.87 MBLicence: Creative Commons: Attribution (CC-BY)

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Cite this

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., ... Hemkens, L. G. (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(1). https://doi.org/10.1186/s12879-021-06829-7

@article{31fffeeccb4c4cf9a7c105e9bb1f9b87,

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

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.",

keywords = "COVID-19/therapy, Humans, Immunization, Passive, Randomized Controlled Trials as Topic, SARS-CoV-2, Treatment Outcome",

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

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doi = "10.1186/s12879-021-06829-7",

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Axfors, C, Janiaud, P, Schmitt, AM, Van't Hooft, J, Smith, ER, Haber, NA, Abayomi, A, Abduljalil, M, Abdulrahman, A, Acosta-Ampudia, Y, Aguilar-Guisado, M, Al-Beidh, F, Alejandria, MM, Alfonso, RN, Ali, M, AlQahtani, M, AlZamrooni, A, Anaya, J-M, Ang, MAC, Aomar, IF, Argumanis, LE, Averyanov, A, Baklaushev, VP, Balionis, O, Benfield, T, Berry, S, Birocco, N, Bonifacio, LB, Bowen, AC, Bown, A, Cabello-Gutierrez, C, Camacho, B, Camacho-Ortiz, A, Campbell-Lee, S, Cao, DH, Cardesa, A, Carnate, JM, Castillo, GJJ, Cavallo, R, Chowdhury, FR, Chowdhury, FUH, Ciccone, G, Cingolani, A, Climacosa, FMM, Compernolle, V, Cortez, CFN, Costa Neto, A, D'Antico, S, Daly, J, Danielle, F, Davis, JS, De Rosa, FG, Denholm, JT, Denkinger, CM, Desmecht, D, Díaz-Coronado, JC, Díaz Ponce-Medrano, JA, Donneau, A-F, Dumagay, TE, Dunachie, S, Dungog, CC, Erinoso, O, Escasa, IMS, Estcourt, LJ, Evans, A, Evasan, ALM, Fareli, CJ, Fernandez-Sanchez, V, Galassi, C, Gallo, JE, Garcia, PJ, Garcia, PL, Garcia, JA, Garigliany, M, Garza-Gonzalez, E, Gauiran, DTV, Gaviria García, PA, Giron-Gonzalez, J-A, Gómez-Almaguer, D, Gordon, AC, Gothot, A, Grass Guaqueta, JS, Green, C, Grimaldi, D, Hammond, NE, Harvala, H, Heralde, FM, Herrick, J, Higgins, AM, Hills, TE, Hines, J, Holm, K, Hoque, A, Hoste, E, Ignacio, JM, Ivanov, AV, Janssen, M, Jennings, JH, Jha, V, King, RAN, Kjeldsen-Kragh, J, Klenerman, P, Kotecha, A, Krapp, F, Labanca, L, Laing, E, Landin-Olsson, M, Laterre, P-F, Lim, L-L, Lim, J, Ljungquist, O, Llaca-Díaz, JM, López-Robles, C, López-Cárdenas, S, Lopez-Plaza, I, Lucero, JAC, Lundgren, M, Macías, J, Maganito, SC, Malundo, AFG, Manrique, RD, Manzini, PM, Marcos, M, Marquez, I, Martínez-Marcos, FJ, Mata, AM, McArthur, CJ, McQuilten, ZK, McVerry, BJ, Menon, DK, Meyfroidt, G, Mirasol, MAL, Misset, B, Molton, JS, Mondragon, AV, Monsalve, DM, Moradi Choghakabodi, P, Morpeth, SC, Mouncey, PR, Moutschen, M, Müller-Tidow, C, Murphy, E, Najdovski, T, Nichol, AD, Nielsen, H, Novak, RM, O'Sullivan, MVN, Olalla, J, Osibogun, A, Osikomaiya, B, Oyonarte, S, Pardo-Oviedo, JM, Patel, MC, Paterson, DL, Peña-Perez, CA, Perez-Calatayud, AA, Pérez-Alba, E, Perkina, A, Perry, N, Pouladzadeh, M, Poyato, I, Price, DJ, Quero, AKH, Rahman, MM, Rahman, MS, Ramesh, M, Ramírez-Santana, C, Rasmussen, M, Rees, MA, Rego, E, Roberts, JA, Roberts, DJ, Rodríguez, Y, Rodríguez-Baño, J, Rogers, BA, Rojas, M, Romero, A, Rowan, KM, Saccona, F, Safdarian, M, Santos, MCM, Sasadeusz, J, Scozzari, G, Shankar-Hari, M, Sharma, G, Snelling, T, Soto, A, Tagayuna, PY, Tang, A, Tatem, G, Teofili, L, Tong, SYC, Turgeon, AF, Veloso, JD, Venkatesh, B, Ventura-Enriquez, Y, Webb, SA, Wiese, L, Wikén, C, Wood, EM, Yusubalieva, GM, Zacharowski, K, Zarychanski, R, Khanna, N, Moher, D, Goodman, SN, Ioannidis, JPA & Hemkens, LG 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, vol. 21, no. 1. https://doi.org/10.1186/s12879-021-06829-7

TY - JOUR

T1 - Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

AU - Axfors, Cathrine

AU - Janiaud, Perrine

AU - Schmitt, Andreas M

AU - Van't Hooft, Janneke

AU - Smith, Emily R

AU - Haber, Noah A

AU - Abayomi, Akin

AU - Abduljalil, Manal

AU - Abdulrahman, Abdulkarim

AU - Acosta-Ampudia, Yeny

AU - Aguilar-Guisado, Manuela

AU - Al-Beidh, Farah

AU - Alejandria, Marissa M

AU - Alfonso, Rachelle N

AU - Ali, Mohammad

AU - AlQahtani, Manaf

AU - AlZamrooni, Alaa

AU - Anaya, Juan-Manuel

AU - Ang, Mark Angelo C

AU - Aomar, Ismael F

AU - Argumanis, Luis E

AU - Averyanov, Alexander

AU - Baklaushev, Vladimir P

AU - Balionis, Olga

AU - Benfield, Thomas

AU - Berry, Scott

AU - Birocco, Nadia

AU - Bonifacio, Lynn B

AU - Bowen, Asha C

AU - Bown, Abbie

AU - Cabello-Gutierrez, Carlos

AU - Camacho, Bernardo

AU - Camacho-Ortiz, Adrian

AU - Campbell-Lee, Sally

AU - Cao, Damon H

AU - Cardesa, Ana

AU - Carnate, Jose M

AU - Castillo, German Jr J

AU - Cavallo, Rossana

AU - Chowdhury, Fazle R

AU - Chowdhury, Forhad U H

AU - Ciccone, Giovannino

AU - Cingolani, Antonella

AU - Climacosa, Fresthel Monica M

AU - Compernolle, Veerle

AU - Cortez, Carlo Francisco N

AU - Costa Neto, Abel

AU - D'Antico, Sergio

AU - Daly, James

AU - Danielle, Franca

AU - Davis, Joshua S

AU - De Rosa, Francesco Giuseppe

AU - Denholm, Justin T

AU - Denkinger, Claudia M

AU - Desmecht, Daniel

AU - Díaz-Coronado, Juan C

AU - Díaz Ponce-Medrano, Juan A

AU - Donneau, Anne-Françoise

AU - Dumagay, Teresita E

AU - Dunachie, Susanna

AU - Dungog, Cecile C

AU - Erinoso, Olufemi

AU - Escasa, Ivy Mae S

AU - Estcourt, Lise J

AU - Evans, Amy

AU - Evasan, Agnes L M

AU - Fareli, Christian J

AU - Fernandez-Sanchez, Veronica

AU - Galassi, Claudia

AU - Gallo, Juan E

AU - Garcia, Patricia J

AU - Garcia, Patricia L

AU - Garcia, Jesus A

AU - Garigliany, Mutien

AU - Garza-Gonzalez, Elvira

AU - Gauiran, Deonne Thaddeus V

AU - Gaviria García, Paula A

AU - Giron-Gonzalez, Jose-Antonio

AU - Gómez-Almaguer, David

AU - Gordon, Anthony C

AU - Gothot, André

AU - Grass Guaqueta, Jeser Santiago

AU - Green, Cameron

AU - Grimaldi, David

AU - Hammond, Naomi E

AU - Harvala, Heli

AU - Heralde, Francisco M

AU - Herrick, Jesica

AU - Higgins, Alisa M

AU - Hills, Thomas E

AU - Hines, Jennifer

AU - Holm, Karin

AU - Hoque, Ashraful

AU - Hoste, Eric

AU - Ignacio, Jose M

AU - Ivanov, Alexander V

AU - Janssen, Maike

AU - Jennings, Jeffrey H

AU - Jha, Vivekanand

AU - King, Ruby Anne N

AU - Kjeldsen-Kragh, Jens

AU - Klenerman, Paul

AU - Kotecha, Aditya

AU - Krapp, Fiorella

AU - Labanca, Luciana

AU - Laing, Emma

AU - Landin-Olsson, Mona

AU - Laterre, Pierre-François

AU - Lim, Lyn-Li

AU - Lim, Jodor

AU - Ljungquist, Oskar

AU - Llaca-Díaz, Jorge M

AU - López-Robles, Concepción

AU - López-Cárdenas, Salvador

AU - Lopez-Plaza, Ileana

AU - Lucero, Josephine Anne C

AU - Lundgren, Maria

AU - Macías, Juan

AU - Maganito, Sandy C

AU - Malundo, Anna Flor G

AU - Manrique, Rubén D

AU - Manzini, Paola M

AU - Marcos, Miguel

AU - Marquez, Ignacio

AU - Martínez-Marcos, Francisco Javier

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AU - McArthur, Colin J

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AU - Mirasol, Ma Angelina L

AU - Misset, Benoît

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AU - Mouncey, Paul R

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AU - Müller-Tidow, Carsten

AU - Murphy, Erin

AU - Najdovski, Tome

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AU - Olalla, Julian

AU - Osibogun, Akin

AU - Osikomaiya, Bodunrin

AU - Oyonarte, Salvador

AU - Pardo-Oviedo, Juan M

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AU - Paterson, David L

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AU - Poyato, Inmaculada

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AU - Rahman, Md S

AU - Ramesh, Mayur

AU - Ramírez-Santana, Carolina

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AU - Roberts, Jason A

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AU - Rodríguez-Baño, Jesús

AU - Rogers, Benjamin A

AU - Rojas, Manuel

AU - Romero, Alberto

AU - Rowan, Kathryn M

AU - Saccona, Fabio

AU - Safdarian, Mehdi

AU - Santos, Maria Clariza M

AU - Sasadeusz, Joe

AU - Scozzari, Gitana

AU - Shankar-Hari, Manu

AU - Sharma, Gorav

AU - Snelling, Thomas

AU - Soto, Alonso

AU - Tagayuna, Pedrito Y

AU - Tang, Amy

AU - Tatem, Geneva

AU - Teofili, Luciana

AU - Tong, Steven Y C

AU - Turgeon, Alexis F

AU - Veloso, Januario D

AU - Venkatesh, Balasubramanian

AU - Ventura-Enriquez, Yanet

AU - Webb, Steve A

AU - Wiese, Lothar

AU - Wikén, Christian

AU - Wood, Erica M

AU - Yusubalieva, Gaukhar M

AU - Zacharowski, Kai

AU - Zarychanski, Ryan

AU - Khanna, Nina

AU - Moher, David

AU - Goodman, Steven N

AU - Ioannidis, John P A

AU - Hemkens, Lars G

PY - 2021/11/20

Y1 - 2021/11/20

N2 - 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.

AB - 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.

KW - COVID-19/therapy

KW - Humans

KW - Immunization

KW - Passive

KW - Randomized Controlled Trials as Topic

KW - SARS-CoV-2

KW - Treatment Outcome

U2 - 10.1186/s12879-021-06829-7

DO - 10.1186/s12879-021-06829-7

M3 - Article

SN - 1471-2334

VL - 21

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

IS - 1

ER -

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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