tetano
Editor, Senior Moderator
BMC Infect Dis
. 2021 Nov 20;21(1):1170.
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[SUP] 1 2 [/SUP], Perrine Janiaud[SUP] #[/SUP][SUP] 3 [/SUP], Andreas M Schmitt[SUP] 3 4 [/SUP], Janneke Van't Hooft[SUP] 5 [/SUP], Emily R Smith[SUP] 6 [/SUP], Noah A Haber[SUP] 1 [/SUP], Akin Abayomi[SUP] 7 [/SUP], Manal Abduljalil[SUP] 8 [/SUP], Abdulkarim Abdulrahman[SUP] 9 10 [/SUP], Yeny Acosta-Ampudia[SUP] 11 [/SUP], Manuela Aguilar-Guisado[SUP] 12 [/SUP], Farah Al-Beidh[SUP] 13 [/SUP], Marissa M Alejandria[SUP] 14 [/SUP], Rachelle N Alfonso[SUP] 15 [/SUP], Mohammad Ali[SUP] 16 [/SUP], Manaf AlQahtani[SUP] 9 17 18 [/SUP], Alaa AlZamrooni[SUP] 19 [/SUP], Juan-Manuel Anaya[SUP] 11 [/SUP], Mark Angelo C Ang[SUP] 20 [/SUP], Ismael F Aomar[SUP] 21 [/SUP], Luis E Argumanis[SUP] 22 [/SUP], Alexander Averyanov[SUP] 23 24 [/SUP], Vladimir P Baklaushev[SUP] 24 25 [/SUP], Olga Balionis[SUP] 23 26 [/SUP], Thomas Benfield[SUP] 27 [/SUP], Scott Berry[SUP] 28 [/SUP], Nadia Birocco[SUP] 29 [/SUP], Lynn B Bonifacio[SUP] 15 [/SUP], Asha C Bowen[SUP] 30 31 32 [/SUP], Abbie Bown[SUP] 33 [/SUP], Carlos Cabello-Gutierrez[SUP] 34 [/SUP], Bernardo Camacho[SUP] 35 [/SUP], Adrian Camacho-Ortiz[SUP] 36 [/SUP], Sally Campbell-Lee[SUP] 37 [/SUP], Damon H Cao[SUP] 38 [/SUP], Ana Cardesa[SUP] 39 [/SUP], Jose M Carnate[SUP] 40 [/SUP], German Jr J Castillo[SUP] 15 [/SUP], Rossana Cavallo[SUP] 41 [/SUP], Fazle R Chowdhury[SUP] 42 [/SUP], Forhad U H Chowdhury[SUP] 43 [/SUP], Giovannino Ciccone[SUP] 44 [/SUP], Antonella Cingolani[SUP] 45 [/SUP], Fresthel Monica M Climacosa[SUP] 46 [/SUP], Veerle Compernolle[SUP] 47 48 [/SUP], Carlo Francisco N Cortez[SUP] 15 [/SUP], Abel Costa Neto[SUP] 49 [/SUP], Sergio D'Antico[SUP] 50 [/SUP], James Daly[SUP] 51 [/SUP], Franca Danielle[SUP] 52 [/SUP], Joshua S Davis[SUP] 30 [/SUP], Francesco Giuseppe De Rosa[SUP] 53 [/SUP], Justin T Denholm[SUP] 54 55 [/SUP], Claudia M Denkinger[SUP] 56 [/SUP], Daniel Desmecht[SUP] 57 [/SUP], Juan C Díaz-Coronado[SUP] 58 [/SUP], Juan A Díaz Ponce-Medrano[SUP] 59 [/SUP], Anne-Françoise Donneau[SUP] 60 [/SUP], Teresita E Dumagay[SUP] 15 [/SUP], Susanna Dunachie[SUP] 16 [/SUP], Cecile C Dungog[SUP] 40 [/SUP], Olufemi Erinoso[SUP] 61 [/SUP], Ivy Mae S Escasa[SUP] 15 [/SUP], Lise J Estcourt[SUP] 62 63 [/SUP], Amy Evans[SUP] 64 [/SUP], Agnes L M Evasan[SUP] 14 [/SUP], Christian J Fareli[SUP] 65 [/SUP], Veronica Fernandez-Sanchez[SUP] 66 [/SUP], Claudia Galassi[SUP] 44 [/SUP], Juan E Gallo[SUP] 67 [/SUP], Patricia J Garcia[SUP] 68 [/SUP], Patricia L Garcia[SUP] 69 [/SUP], Jesus A Garcia[SUP] 70 [/SUP], Mutien Garigliany[SUP] 57 [/SUP], Elvira Garza-Gonzalez[SUP] 36 [/SUP], Deonne Thaddeus V Gauiran[SUP] 15 [/SUP], Paula A Gaviria García[SUP] 35 [/SUP], Jose-Antonio Giron-Gonzalez[SUP] 71 [/SUP], David Gómez-Almaguer[SUP] 72 [/SUP], Anthony C Gordon[SUP] 13 73 [/SUP], André Gothot[SUP] 74 [/SUP], Jeser Santiago Grass Guaqueta[SUP] 35 [/SUP], Cameron Green[SUP] 75 [/SUP], David Grimaldi[SUP] 76 [/SUP], Naomi E Hammond[SUP] 77 [/SUP], Heli Harvala[SUP] 78 [/SUP], Francisco M Heralde[SUP] 79 [/SUP], Jesica Herrick[SUP] 80 [/SUP], Alisa M Higgins[SUP] 75 [/SUP], Thomas E Hills[SUP] 81 82 [/SUP], Jennifer Hines[SUP] 83 [/SUP], Karin Holm[SUP] 84 85 [/SUP], Ashraful Hoque[SUP] 86 [/SUP], Eric Hoste[SUP] 87 [/SUP], Jose M Ignacio[SUP] 88 [/SUP], Alexander V Ivanov[SUP] 89 [/SUP], Maike Janssen[SUP] 90 [/SUP], Jeffrey H Jennings[SUP] 83 [/SUP], Vivekanand Jha[SUP] 91 92 93 [/SUP], Ruby Anne N King[SUP] 79 [/SUP], Jens Kjeldsen-Kragh[SUP] 94 [/SUP], Paul Klenerman[SUP] 16 [/SUP], Aditya Kotecha[SUP] 83 [/SUP], Fiorella Krapp[SUP] 95 [/SUP], Luciana Labanca[SUP] 52 [/SUP], Emma Laing[SUP] 64 [/SUP], Mona Landin-Olsson[SUP] 96 97 [/SUP], Pierre-François Laterre[SUP] 98 [/SUP], Lyn-Li Lim[SUP] 99 [/SUP], Jodor Lim[SUP] 14 [/SUP], Oskar Ljungquist[SUP] 100 [/SUP], Jorge M Llaca-Díaz[SUP] 101 [/SUP], Concepción López-Robles[SUP] 102 [/SUP], Salvador López-Cárdenas[SUP] 103 [/SUP], Ileana Lopez-Plaza[SUP] 104 [/SUP], Josephine Anne C Lucero[SUP] 15 [/SUP], Maria Lundgren[SUP] 94 [/SUP], Juan Macías[SUP] 105 [/SUP], Sandy C Maganito[SUP] 40 [/SUP], Anna Flor G Malundo[SUP] 14 [/SUP], Rubén D Manrique[SUP] 106 [/SUP], Paola M Manzini[SUP] 50 [/SUP], Miguel Marcos[SUP] 107 [/SUP], Ignacio Marquez[SUP] 108 [/SUP], Francisco Javier Martínez-Marcos[SUP] 109 [/SUP], Ana M Mata[SUP] 110 [/SUP], Colin J McArthur[SUP] 111 [/SUP], Zoe K McQuilten[SUP] 112 113 [/SUP], Bryan J McVerry[SUP] 114 [/SUP], David K Menon[SUP] 115 [/SUP], Geert Meyfroidt[SUP] 116 [/SUP], Ma Angelina L Mirasol[SUP] 15 [/SUP], Benoît Misset[SUP] 117 [/SUP], James S Molton[SUP] 118 [/SUP], Alric V Mondragon[SUP] 119 [/SUP], Diana M Monsalve[SUP] 11 [/SUP], Parastoo Moradi Choghakabodi[SUP] 120 121 [/SUP], Susan C Morpeth[SUP] 122 [/SUP], Paul R Mouncey[SUP] 123 [/SUP], Michel Moutschen[SUP] 117 [/SUP], Carsten Müller-Tidow[SUP] 90 [/SUP], Erin Murphy[SUP] 83 [/SUP], Tome Najdovski[SUP] 124 [/SUP], Alistair D Nichol[SUP] 125 126 127 [/SUP], Henrik Nielsen[SUP] 128 [/SUP], Richard M Novak[SUP] 80 [/SUP], Matthew V N O'Sullivan[SUP] 129 130 131 [/SUP], Julian Olalla[SUP] 132 [/SUP], Akin Osibogun[SUP] 133 [/SUP], Bodunrin Osikomaiya[SUP] 7 [/SUP], Salvador Oyonarte[SUP] 134 [/SUP], Juan M Pardo-Oviedo[SUP] 135 [/SUP], Mahesh C Patel[SUP] 80 [/SUP], David L Paterson[SUP] 136 [/SUP], Carlos A Peña-Perez[SUP] 137 [/SUP], Angel A Perez-Calatayud[SUP] 138 [/SUP], Eduardo Pérez-Alba[SUP] 36 [/SUP], Anastasia Perkina[SUP] 23 26 [/SUP], Naomi Perry[SUP] 55 [/SUP], Mandana Pouladzadeh[SUP] 139 [/SUP], Inmaculada Poyato[SUP] 140 [/SUP], David J Price[SUP] 141 142 [/SUP], Anne Kristine H Quero[SUP] 15 [/SUP], Md M Rahman[SUP] 43 [/SUP], Md S Rahman[SUP] 143 [/SUP], Mayur Ramesh[SUP] 144 [/SUP], Carolina Ramírez-Santana[SUP] 11 [/SUP], Magnus Rasmussen[SUP] 84 85 [/SUP], Megan A Rees[SUP] 145 146 [/SUP], Eduardo Rego[SUP] 49 [/SUP], Jason A Roberts[SUP] 135 147 148 [/SUP], David J Roberts[SUP] 63 149 [/SUP], Yhojan Rodríguez[SUP] 11 150 [/SUP], Jesús Rodríguez-Baño[SUP] 151 152 [/SUP], Benjamin A Rogers[SUP] 153 154 [/SUP], Manuel Rojas[SUP] 11 [/SUP], Alberto Romero[SUP] 155 [/SUP], Kathryn M Rowan[SUP] 156 [/SUP], Fabio Saccona[SUP] 44 [/SUP], Mehdi Safdarian[SUP] 157 [/SUP], Maria Clariza M Santos[SUP] 15 [/SUP], Joe Sasadeusz[SUP] 54 55 [/SUP], Gitana Scozzari[SUP] 158 [/SUP], Manu Shankar-Hari[SUP] 159 160 [/SUP], Gorav Sharma[SUP] 83 [/SUP], Thomas Snelling[SUP] 30 31 161 162 [/SUP], Alonso Soto[SUP] 163 164 [/SUP], Pedrito Y Tagayuna[SUP] 40 [/SUP], Amy Tang[SUP] 165 [/SUP], Geneva Tatem[SUP] 83 [/SUP], Luciana Teofili[SUP] 166 [/SUP], Steven Y C Tong[SUP] 167 168 [/SUP], Alexis F Turgeon[SUP] 169 [/SUP], Januario D Veloso[SUP] 15 [/SUP], Balasubramanian Venkatesh[SUP] 77 170 171 [/SUP], Yanet Ventura-Enriquez[SUP] 172 [/SUP], Steve A Webb[SUP] 125 173 [/SUP], Lothar Wiese[SUP] 174 [/SUP], Christian Wikén[SUP] 85 [/SUP], Erica M Wood[SUP] 175 [/SUP], Gaukhar M Yusubalieva[SUP] 25 [/SUP], Kai Zacharowski[SUP] 176 [/SUP], Ryan Zarychanski[SUP] 177 [/SUP], Nina Khanna[SUP] 178 [/SUP], David Moher[SUP] 179 [/SUP], Steven N Goodman[SUP] 1 180 181 [/SUP], John P A Ioannidis[SUP] 1 181 182 183 184 [/SUP], Lars G Hemkens[SUP] 185 186 187 [/SUP]
Affiliations
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 (I[SUP]2[/SUP] = 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; Convalescent plasma; Meta-analysis; SARS-CoV-2.
. 2021 Nov 20;21(1):1170.
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[SUP] 1 2 [/SUP], Perrine Janiaud[SUP] #[/SUP][SUP] 3 [/SUP], Andreas M Schmitt[SUP] 3 4 [/SUP], Janneke Van't Hooft[SUP] 5 [/SUP], Emily R Smith[SUP] 6 [/SUP], Noah A Haber[SUP] 1 [/SUP], Akin Abayomi[SUP] 7 [/SUP], Manal Abduljalil[SUP] 8 [/SUP], Abdulkarim Abdulrahman[SUP] 9 10 [/SUP], Yeny Acosta-Ampudia[SUP] 11 [/SUP], Manuela Aguilar-Guisado[SUP] 12 [/SUP], Farah Al-Beidh[SUP] 13 [/SUP], Marissa M Alejandria[SUP] 14 [/SUP], Rachelle N Alfonso[SUP] 15 [/SUP], Mohammad Ali[SUP] 16 [/SUP], Manaf AlQahtani[SUP] 9 17 18 [/SUP], Alaa AlZamrooni[SUP] 19 [/SUP], Juan-Manuel Anaya[SUP] 11 [/SUP], Mark Angelo C Ang[SUP] 20 [/SUP], Ismael F Aomar[SUP] 21 [/SUP], Luis E Argumanis[SUP] 22 [/SUP], Alexander Averyanov[SUP] 23 24 [/SUP], Vladimir P Baklaushev[SUP] 24 25 [/SUP], Olga Balionis[SUP] 23 26 [/SUP], Thomas Benfield[SUP] 27 [/SUP], Scott Berry[SUP] 28 [/SUP], Nadia Birocco[SUP] 29 [/SUP], Lynn B Bonifacio[SUP] 15 [/SUP], Asha C Bowen[SUP] 30 31 32 [/SUP], Abbie Bown[SUP] 33 [/SUP], Carlos Cabello-Gutierrez[SUP] 34 [/SUP], Bernardo Camacho[SUP] 35 [/SUP], Adrian Camacho-Ortiz[SUP] 36 [/SUP], Sally Campbell-Lee[SUP] 37 [/SUP], Damon H Cao[SUP] 38 [/SUP], Ana Cardesa[SUP] 39 [/SUP], Jose M Carnate[SUP] 40 [/SUP], German Jr J Castillo[SUP] 15 [/SUP], Rossana Cavallo[SUP] 41 [/SUP], Fazle R Chowdhury[SUP] 42 [/SUP], Forhad U H Chowdhury[SUP] 43 [/SUP], Giovannino Ciccone[SUP] 44 [/SUP], Antonella Cingolani[SUP] 45 [/SUP], Fresthel Monica M Climacosa[SUP] 46 [/SUP], Veerle Compernolle[SUP] 47 48 [/SUP], Carlo Francisco N Cortez[SUP] 15 [/SUP], Abel Costa Neto[SUP] 49 [/SUP], Sergio D'Antico[SUP] 50 [/SUP], James Daly[SUP] 51 [/SUP], Franca Danielle[SUP] 52 [/SUP], Joshua S Davis[SUP] 30 [/SUP], Francesco Giuseppe De Rosa[SUP] 53 [/SUP], Justin T Denholm[SUP] 54 55 [/SUP], Claudia M Denkinger[SUP] 56 [/SUP], Daniel Desmecht[SUP] 57 [/SUP], Juan C Díaz-Coronado[SUP] 58 [/SUP], Juan A Díaz Ponce-Medrano[SUP] 59 [/SUP], Anne-Françoise Donneau[SUP] 60 [/SUP], Teresita E Dumagay[SUP] 15 [/SUP], Susanna Dunachie[SUP] 16 [/SUP], Cecile C Dungog[SUP] 40 [/SUP], Olufemi Erinoso[SUP] 61 [/SUP], Ivy Mae S Escasa[SUP] 15 [/SUP], Lise J Estcourt[SUP] 62 63 [/SUP], Amy Evans[SUP] 64 [/SUP], Agnes L M Evasan[SUP] 14 [/SUP], Christian J Fareli[SUP] 65 [/SUP], Veronica Fernandez-Sanchez[SUP] 66 [/SUP], Claudia Galassi[SUP] 44 [/SUP], Juan E Gallo[SUP] 67 [/SUP], Patricia J Garcia[SUP] 68 [/SUP], Patricia L Garcia[SUP] 69 [/SUP], Jesus A Garcia[SUP] 70 [/SUP], Mutien Garigliany[SUP] 57 [/SUP], Elvira Garza-Gonzalez[SUP] 36 [/SUP], Deonne Thaddeus V Gauiran[SUP] 15 [/SUP], Paula A Gaviria García[SUP] 35 [/SUP], Jose-Antonio Giron-Gonzalez[SUP] 71 [/SUP], David Gómez-Almaguer[SUP] 72 [/SUP], Anthony C Gordon[SUP] 13 73 [/SUP], André Gothot[SUP] 74 [/SUP], Jeser Santiago Grass Guaqueta[SUP] 35 [/SUP], Cameron Green[SUP] 75 [/SUP], David Grimaldi[SUP] 76 [/SUP], Naomi E Hammond[SUP] 77 [/SUP], Heli Harvala[SUP] 78 [/SUP], Francisco M Heralde[SUP] 79 [/SUP], Jesica Herrick[SUP] 80 [/SUP], Alisa M Higgins[SUP] 75 [/SUP], Thomas E Hills[SUP] 81 82 [/SUP], Jennifer Hines[SUP] 83 [/SUP], Karin Holm[SUP] 84 85 [/SUP], Ashraful Hoque[SUP] 86 [/SUP], Eric Hoste[SUP] 87 [/SUP], Jose M Ignacio[SUP] 88 [/SUP], Alexander V Ivanov[SUP] 89 [/SUP], Maike Janssen[SUP] 90 [/SUP], Jeffrey H Jennings[SUP] 83 [/SUP], Vivekanand Jha[SUP] 91 92 93 [/SUP], Ruby Anne N King[SUP] 79 [/SUP], Jens Kjeldsen-Kragh[SUP] 94 [/SUP], Paul Klenerman[SUP] 16 [/SUP], Aditya Kotecha[SUP] 83 [/SUP], Fiorella Krapp[SUP] 95 [/SUP], Luciana Labanca[SUP] 52 [/SUP], Emma Laing[SUP] 64 [/SUP], Mona Landin-Olsson[SUP] 96 97 [/SUP], Pierre-François Laterre[SUP] 98 [/SUP], Lyn-Li Lim[SUP] 99 [/SUP], Jodor Lim[SUP] 14 [/SUP], Oskar Ljungquist[SUP] 100 [/SUP], Jorge M Llaca-Díaz[SUP] 101 [/SUP], Concepción López-Robles[SUP] 102 [/SUP], Salvador López-Cárdenas[SUP] 103 [/SUP], Ileana Lopez-Plaza[SUP] 104 [/SUP], Josephine Anne C Lucero[SUP] 15 [/SUP], Maria Lundgren[SUP] 94 [/SUP], Juan Macías[SUP] 105 [/SUP], Sandy C Maganito[SUP] 40 [/SUP], Anna Flor G Malundo[SUP] 14 [/SUP], Rubén D Manrique[SUP] 106 [/SUP], Paola M Manzini[SUP] 50 [/SUP], Miguel Marcos[SUP] 107 [/SUP], Ignacio Marquez[SUP] 108 [/SUP], Francisco Javier Martínez-Marcos[SUP] 109 [/SUP], Ana M Mata[SUP] 110 [/SUP], Colin J McArthur[SUP] 111 [/SUP], Zoe K McQuilten[SUP] 112 113 [/SUP], Bryan J McVerry[SUP] 114 [/SUP], David K Menon[SUP] 115 [/SUP], Geert Meyfroidt[SUP] 116 [/SUP], Ma Angelina L Mirasol[SUP] 15 [/SUP], Benoît Misset[SUP] 117 [/SUP], James S Molton[SUP] 118 [/SUP], Alric V Mondragon[SUP] 119 [/SUP], Diana M Monsalve[SUP] 11 [/SUP], Parastoo Moradi Choghakabodi[SUP] 120 121 [/SUP], Susan C Morpeth[SUP] 122 [/SUP], Paul R Mouncey[SUP] 123 [/SUP], Michel Moutschen[SUP] 117 [/SUP], Carsten Müller-Tidow[SUP] 90 [/SUP], Erin Murphy[SUP] 83 [/SUP], Tome Najdovski[SUP] 124 [/SUP], Alistair D Nichol[SUP] 125 126 127 [/SUP], Henrik Nielsen[SUP] 128 [/SUP], Richard M Novak[SUP] 80 [/SUP], Matthew V N O'Sullivan[SUP] 129 130 131 [/SUP], Julian Olalla[SUP] 132 [/SUP], Akin Osibogun[SUP] 133 [/SUP], Bodunrin Osikomaiya[SUP] 7 [/SUP], Salvador Oyonarte[SUP] 134 [/SUP], Juan M Pardo-Oviedo[SUP] 135 [/SUP], Mahesh C Patel[SUP] 80 [/SUP], David L Paterson[SUP] 136 [/SUP], Carlos A Peña-Perez[SUP] 137 [/SUP], Angel A Perez-Calatayud[SUP] 138 [/SUP], Eduardo Pérez-Alba[SUP] 36 [/SUP], Anastasia Perkina[SUP] 23 26 [/SUP], Naomi Perry[SUP] 55 [/SUP], Mandana Pouladzadeh[SUP] 139 [/SUP], Inmaculada Poyato[SUP] 140 [/SUP], David J Price[SUP] 141 142 [/SUP], Anne Kristine H Quero[SUP] 15 [/SUP], Md M Rahman[SUP] 43 [/SUP], Md S Rahman[SUP] 143 [/SUP], Mayur Ramesh[SUP] 144 [/SUP], Carolina Ramírez-Santana[SUP] 11 [/SUP], Magnus Rasmussen[SUP] 84 85 [/SUP], Megan A Rees[SUP] 145 146 [/SUP], Eduardo Rego[SUP] 49 [/SUP], Jason A Roberts[SUP] 135 147 148 [/SUP], David J Roberts[SUP] 63 149 [/SUP], Yhojan Rodríguez[SUP] 11 150 [/SUP], Jesús Rodríguez-Baño[SUP] 151 152 [/SUP], Benjamin A Rogers[SUP] 153 154 [/SUP], Manuel Rojas[SUP] 11 [/SUP], Alberto Romero[SUP] 155 [/SUP], Kathryn M Rowan[SUP] 156 [/SUP], Fabio Saccona[SUP] 44 [/SUP], Mehdi Safdarian[SUP] 157 [/SUP], Maria Clariza M Santos[SUP] 15 [/SUP], Joe Sasadeusz[SUP] 54 55 [/SUP], Gitana Scozzari[SUP] 158 [/SUP], Manu Shankar-Hari[SUP] 159 160 [/SUP], Gorav Sharma[SUP] 83 [/SUP], Thomas Snelling[SUP] 30 31 161 162 [/SUP], Alonso Soto[SUP] 163 164 [/SUP], Pedrito Y Tagayuna[SUP] 40 [/SUP], Amy Tang[SUP] 165 [/SUP], Geneva Tatem[SUP] 83 [/SUP], Luciana Teofili[SUP] 166 [/SUP], Steven Y C Tong[SUP] 167 168 [/SUP], Alexis F Turgeon[SUP] 169 [/SUP], Januario D Veloso[SUP] 15 [/SUP], Balasubramanian Venkatesh[SUP] 77 170 171 [/SUP], Yanet Ventura-Enriquez[SUP] 172 [/SUP], Steve A Webb[SUP] 125 173 [/SUP], Lothar Wiese[SUP] 174 [/SUP], Christian Wikén[SUP] 85 [/SUP], Erica M Wood[SUP] 175 [/SUP], Gaukhar M Yusubalieva[SUP] 25 [/SUP], Kai Zacharowski[SUP] 176 [/SUP], Ryan Zarychanski[SUP] 177 [/SUP], Nina Khanna[SUP] 178 [/SUP], David Moher[SUP] 179 [/SUP], Steven N Goodman[SUP] 1 180 181 [/SUP], John P A Ioannidis[SUP] 1 181 182 183 184 [/SUP], Lars G Hemkens[SUP] 185 186 187 [/SUP]
Affiliations
- PMID: 34800996
- DOI: 10.1186/s12879-021-06829-7
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 (I[SUP]2[/SUP] = 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; Convalescent plasma; Meta-analysis; SARS-CoV-2.