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1. Cell fate choices and developmental competence in the avian head mesoderm

Author

Alzamrooni, Afnan Mahmood Ahmed Mustafa, Dietrich, Susanne, Myers, Fiona, and Schubert, Frank

Abstract

Cardiovascular diseases are a leading cause of mortality world-wide. The general approach to managing the disease burden is to reduce risk factors and to control symptoms. However, when a heart attack occurs and cardiomyocytes perish as a result, there currently is no feasible strategy to replace the lost cells and to cure the disease. Progress has been made to generate cardiomyocytes in vitro, but these cells fail to integrate and beat according to the rhythm set by the existing heart. Yet in the embryo there are cells that achieve this; the secondary heart field cells. These cells are added onto the primitive heart over a prolonged time during embryogenesis and follow the beat set by the existing cells. The challenge is to molecularly characterise these cells such that the recruitment and integration process can be recapitulated in a patient. Both the primary heart field cells for the primitive heart and the secondary heart field cells that are added on later arise from the embryonic head mesoderm. Previous studies showed that initially, the entire head mesoderm is cardiac competent. Yet eventually, cells from the head mesoderm also form non-cardiac tissues such as skeletal muscle. It is therefore important to determine the time window in which the head mesoderm is heart-competent as stepping stone towards further molecular analyses. The chicken embryo is used as an established model for human heart development. Bone morphogenetic protein (BMP) are crucial for the induction of cardiogenesis and cardiomyocyte differentiation. BMP is loaded onto carrier beads and is implanted into the paraxial aspect of the head mesoderm that is fated to produce non-cardiogenic cell types. The experiment was conducted at several time points in development; embryos were analysed by in situ hybridisation for the expression of various cardiac and non-cardiac marker genes. It was found that the head mesoderm has full cardiac competence up to stages HH5/6 of development, which is 12 hours after the head mesoderm first formed at HH3/4. In the subsequent hours, cardiac competence declines as successively fewer cardiac markers respond to BMP. Instead, markers typical for head skeletal muscle precursors become activated, suggesting a shift from cardiac to myogenic competence. This suggest that the analysis of the molecular control and the underlying mechanism of the decline of cardiac competence has to focus onto the early head mesoderm.

Published
2023

3. Metabolic Adaptations in Adult Spiny Mouse (Acomys) Cardiomyocytes Facilitate Enhanced Cardiac Recovery Following Myocardial Infarction

Author

Kuppa, Annapurna, primary, Alzamrooni, Afnan, additional, Suhan, Tahra, additional, Chaudhary, Rajesh, additional, Lopez, Rachel, additional, Collins, Nicole, additional, Van Den Bergh, Fran, additional, Abouleisa, Riham, additional, Wang, Harrison, additional, Mohamed, Tamer, additional, Satin, Jonathan, additional, Lyssiotis, Costas A, additional, Beard, Dan, additional, and Abdel-Latif, Ahmed, additional

Published
2024
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5. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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, and Lars G. Hemkens

Subjects
Meta-analysis, SARS-CoV-2, COVID-19, Convalescent plasma, Infectious and parasitic diseases, RC109-216
Abstract

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.

Published
2021
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6. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, 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 Mae 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 Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose-Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, 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 Anne 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 Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina 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 Kristine 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 Clariza 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., and Hemkens, Lars G.

Published
2021
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9. Ileal lactobezoar in extreme premature infant complicated by intestinal perforation: A case report

Author

Mohamed Elkhouli, Farid Aleali, Ayah Alzamrooni, Priscilla Chiu, and Estelle Gauda

Subjects
Surgery
Abstract

Lactobezor is a rare complication that has been reported more in the stomach, however it may be located anywhere in the intestine.Reported here, is a case of ileal lactobezoar which was complicated by perforation and was mimicking necrotizing enterocolitis in presentation, ex preterm (26 weeks) male infant who presented at day of life 18th (2 days after BM fortification) with hemodynamic instability and intestinal perforation, which was diagnosed by Abdominal X-ray and Ultrasound necessitating urgent laparotomy.Laparotomy revealed an area of ileal perforation and an inspissated mass which was confirmed to be lactobezoar by pathology, ileostomy was performed. The baby had an acute postoperative status of hypovolemic shock which was managed clinically, then was restarted on feeds, and the stoma was reversed 9 weeks later.Lactobezoar, although rare, but numbers increased especially with the rise in numbers of extremely preterm infants worldwide, it most commonly presents later in life but in some cases, such as our case it may happen in 1st 2-3 weeks after birth and may cause significant complications as perforation making its differentiation from common GI problems in neonates as NEC more challenging.

Published
2022

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

Author

Erin Murphy, Franca Danielle, Carlos Cabello-Gutierrez, Jason A. Roberts, Juan-Manuel Anaya, Fabio Saccona, Paula A. Gaviria García, Geert Meyfroidt, Olufemi Erinoso, Joshua S. Davis, Oskar Ljungquist, Rossana Cavallo, Kathryn M Rowan, James S. Molton, Alberto Romero, Gitana Scozzari, Alexander V. Ivanov, Manaf AlQahtani, Eduardo Rego, Luis E. Argumanis, Jeffrey H. Jennings, German Jr J. Castillo, Deonne Thaddeus V. Gauiran, M. Rahman, Anne Françoise Donneau, Josephine Anne C. Lucero, Christian J. Fareli, Fresthel Monica M. Climacosa, Adrián Camacho-Ortiz, Aditya Kotecha, Nadia Birocco, Damon H. Cao, David Price, Joe Sasadeusz, Jose M. Ignacio, Antonella Cingolani, Abdulkarim Abdulrahman, Alisa Higgins, Perrine Janiaud, James Daly, Eduardo Perez-Alba, Henrik Nielsen, Cecile C. Dungog, Paul Klenerman, Fazle Rabbi Chowdhury, Diana M. Monsalve, Claudia M. Denkinger, Andreas M. Schmitt, Lyn Li Lim, Heli Harvala, Mahesh C. Patel, Alexis F. Turgeon, Akin Abayomi, Vladimir P. Baklaushev, Rachelle N. Alfonso, Fiorella Krapp, Juan E. Gallo, Januario D. Veloso, Lynn B. Bonifacio, Bryan J. McVerry, Mehdi Safdarian, Ismael F. Aomar, Yanet Ventura-Enriquez, Alric V. Mondragon, Pedrito Y. Tagayuna, Mona Landin-Olsson, Yhojan Rodríguez, Nina Khanna, André Gothot, David Grimaldi, Forhad Hossain Chowdhury, Paola M. Manzini, Farah Al-Beidh, Vivekanand Jha, Ángel Augusto Pérez-Calatayud, Inmaculada Poyato, Salvador Oyonarte, Anne Kristine H. Quero, Manuel Rojas, Carlo Francisco N. Cortez, Bernardo Camacho, Elvira Garza-González, Susan C. Morpeth, Steve Webb, Anastasia Perkina, Marissa M. Alejandria, Emma Laing, Matthew V. N. O'Sullivan, Naomi Perry, Karin Holm, Alexander Averyanov, John P. A. Ioannidis, Mutien Garigliany, Patricia J. Garcia, Ashraful Hoque, Ivy Mae S. Escasa, Jodor Lim, Paul R. Mouncey, Balasubramanian Venkatesh, Kai Zacharowski, Lise J Estcourt, Concepción López-Robles, Teresita E. Dumagay, Megan Rees, Emily R. Smith, Juan C. Díaz-Coronado, Jorge M. Llaca-Díaz, Julián Olalla, Janneke van 't Hooft, S. Rahman, Michel Moutschen, Pierre-François Laterre, Carlos A. Peña-Perez, Geneva Tatem, Mandana Pouladzadeh, Sandy C. Maganito, Lars G. Hemkens, Benjamin A. Rogers, Ryan Zarychanski, Mark Angelo C. Ang, Amy Evans, Susanna Dunachie, Tom Snelling, Claudia Galassi, Anthony C. Gordon, Ana Cardesa, Jesus A. Garcia, Colin McArthur, Akin Osibogun, Zoe McQuilten, David Moher, Juan Mauricio Pardo-Oviedo, Benoît Misset, Naomi E Hammond, Maria Clariza M. Santos, Maria Lundgren, Yeny Acosta-Ampudia, Steven Y. C. Tong, Ana M. Mata, Gorav Sharma, Sergio D’Antico, Maike Janssen, Alistair Nichol, Christian Wikén, Noah Haber, Alaa AlZamrooni, Alonso Soto, Jens Kjeldsen-Kragh, Salvador López-Cárdenas, Patricia L. Garcia, Manu Shankar-Hari, Rubén D. Manrique, Ileana Lopez-Plaza, Sally Campbell-Lee, Giovannino Ciccone, Jeser Santiago Grass Guaqueta, Miguel Marcos, Francisco M. Heralde, Richard M. Novak, Eric Hoste, Asha C. Bowen, Ignacio Marquez, Abel Costa Neto, David K. Menon, Ma Angelina L. Mirasol, Magnus Rasmussen, David Gómez-Almaguer, Erica M. Wood, Jennifer Hines, Daniel Desmecht, Olga Balionis, Thomas Benfield, Veronica Fernandez-Sanchez, Ruby Anne N King, Jesús Rodríguez-Baño, David L. Paterson, Jose M. Carnate, Carolina Ramírez-Santana, Lothar Wiese, Luciana Labanca, Cameron Green, Jose Antonio Giron-Gonzalez, Abbie Bown, Scott Berry, Agnes L.M. Evasan, Juan A. Díaz Ponce-Medrano, Manal Abduljalil, Anna Flor G. Malundo, Justin T Denholm, Amy Tang, Juan Macías, Luciana Teofili, Veerle Compernolle, Steven N. Goodman, Manuela Aguilar-Guisado, Thomas Hills, Cathrine Axfors, Tome Najdovski, Jesica A. Herrick, Bodunrin Osikomaiya, David J. Roberts, Mayur Ramesh, Francesco Giuseppe De Rosa, Francisco Javier Martínez-Marcos, Mohammed K. Ali, Gaukhar M. Yusubalieva, Carsten Müller-Tidow, Parastoo Moradi Choghakabodi, AlQahtani, Manaf [0000-0002-1523-0429], Hills, Thomas E [0000-0003-0322-5822], Hoste, Eric [0000-0001-9301-8055], Price, David J [0000-0003-0076-3123], Yusubalieva, Gaukhar M [0000-0003-3056-4889], Apollo - University of Cambridge Repository, University of Manitoba, NIHR, National Institute for Health Research, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
medicine.medical_specialty, Infectious Medicine, Convalescent plasma, Infektionsmedicin, Infectious and parasitic diseases, RC109-216, 030204 cardiovascular system & hematology, Passive, Placebo, Microbiology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 1108 Medical Microbiology, law, Internal medicine, Medicine and Health Sciences, Medicine, Humans, 030212 general & internal medicine, COVID-19 Serotherapy, Randomized Controlled Trials as Topic, Science & Technology, business.industry, SARS-CoV-2, Immunization, Passive, COVID-19, 1103 Clinical Sciences, Intensive care unit, Confidence interval, 3. Good health, TIME, Clinical trial, Settore MED/15 - MALATTIE DEL SANGUE, Meta-analysis, Clinical research, Treatment Outcome, Infectious Diseases, Relative risk, Immunization, business, Life Sciences & Biomedicine, Research Article, 0605 Microbiology, COVID-19/therapy
Abstract

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., 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., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

Published
2021
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11. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Author

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., Aomar I.F., Argumanis L.E., Averyanov A., Baklaushev V.P., Balionis O., Benfield T., Berry S., Birocco N., Bonifacio L.B., Bowen A.C., Bown A., Cabello-Gutierrez C., Camacho B., Camacho-Ortiz A., Campbell-Lee S., Cao D.H., Cardesa A., Carnate J.M., Castillo G.J.J., Cavallo R., Chowdhury F.R., Chowdhury F.U.H., Ciccone G., Cingolani A., Climacosa F.M.M., Compernolle V., Cortez C.F.N., Costa Neto A., D'Antico S., Daly J., Danielle F., Davis J.S., De Rosa F.G., Denholm J.T., Denkinger C.M., Desmecht D., Diaz-Coronado J.C., Diaz Ponce-Medrano J.A., Donneau A.-F., Dumagay T.E., Dunachie S., Dungog C.C., Erinoso O., Escasa I.M.S., Estcourt L.J., Evans A., Evasan A.L.M., Fareli C.J., Fernandez-Sanchez V., Galassi C., Gallo J.E., Garcia P.J., Garcia P.L., Garcia J.A., Garigliany M., Garza-Gonzalez E., Gauiran D.T.V., Gaviria Garcia P.A., Giron-Gonzalez J.-A., Gomez-Almaguer D., Gordon A.C., Gothot A., Grass Guaqueta J.S., Green C., Grimaldi D., Hammond N.E., Harvala H., Heralde F.M., Herrick J., Higgins A.M., Hills T.E., Hines J., Holm K., Hoque A., Hoste E., Ignacio J.M., Ivanov A.V., Janssen M., Jennings J.H., Jha V., King R.A.N., 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-Diaz J.M., Lopez-Robles C., Lopez-Cardenas S., Lopez-Plaza I., Lucero J.A.C., Lundgren M., Macias J., Maganito S.C., Malundo A.F.G., Manrique R.D., Manzini P.M., Marcos M., Marquez I., Martinez-Marcos F.J., Mata A.M., McArthur C.J., McQuilten Z.K., McVerry B.J., Menon D.K., Meyfroidt G., Mirasol M.A.L., Misset B., Molton J.S., Mondragon A.V., Monsalve D.M., Moradi Choghakabodi P., Morpeth S.C., Mouncey P.R., Moutschen M., Muller-Tidow C., Murphy E., Najdovski T., Nichol A.D., Nielsen H., Novak R.M., O'Sullivan M.V.N., Olalla J., Osibogun A., Osikomaiya B., Oyonarte S., Pardo-Oviedo J.M., Patel M.C., Paterson D.L., Pena-Perez C.A., Perez-Calatayud A.A., Perez-Alba E., Perkina A., Perry N., Pouladzadeh M., Poyato I., Price D.J., Quero A.K.H., Rahman M.M., Rahman M.S., Ramesh M., Ramirez-Santana C., Rasmussen M., Rees M.A., Rego E., Roberts J.A., Roberts D.J., Rodriguez Y., Rodriguez-Bano J., Rogers B.A., Rojas M., Romero A., Rowan K.M., Saccona F., Safdarian M., Santos M.C.M., Sasadeusz J., Scozzari G., Shankar-Hari M., Sharma G., Snelling T., Soto A., Tagayuna P.Y., Tang A., Tatem G., Teofili L., Tong S.Y.C., Turgeon A.F., Veloso J.D., Venkatesh B., Ventura-Enriquez Y., Webb S.A., Wiese L., Wiken C., Wood E.M., Yusubalieva G.M., Zacharowski K., Zarychanski R., Khanna N., Moher D., Goodman S.N., Ioannidis J.P.A., Hemkens L.G., 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., Aomar I.F., Argumanis L.E., Averyanov A., Baklaushev V.P., Balionis O., Benfield T., Berry S., Birocco N., Bonifacio L.B., Bowen A.C., Bown A., Cabello-Gutierrez C., Camacho B., Camacho-Ortiz A., Campbell-Lee S., Cao D.H., Cardesa A., Carnate J.M., Castillo G.J.J., Cavallo R., Chowdhury F.R., Chowdhury F.U.H., Ciccone G., Cingolani A., Climacosa F.M.M., Compernolle V., Cortez C.F.N., Costa Neto A., D'Antico S., Daly J., Danielle F., Davis J.S., De Rosa F.G., Denholm J.T., Denkinger C.M., Desmecht D., Diaz-Coronado J.C., Diaz Ponce-Medrano J.A., Donneau A.-F., Dumagay T.E., Dunachie S., Dungog C.C., Erinoso O., Escasa I.M.S., Estcourt L.J., Evans A., Evasan A.L.M., Fareli C.J., Fernandez-Sanchez V., Galassi C., Gallo J.E., Garcia P.J., Garcia P.L., Garcia J.A., Garigliany M., Garza-Gonzalez E., Gauiran D.T.V., Gaviria Garcia P.A., Giron-Gonzalez J.-A., Gomez-Almaguer D., Gordon A.C., Gothot A., Grass Guaqueta J.S., Green C., Grimaldi D., Hammond N.E., Harvala H., Heralde F.M., Herrick J., Higgins A.M., Hills T.E., Hines J., Holm K., Hoque A., Hoste E., Ignacio J.M., Ivanov A.V., Janssen M., Jennings J.H., Jha V., King R.A.N., 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-Diaz J.M., Lopez-Robles C., Lopez-Cardenas S., Lopez-Plaza I., Lucero J.A.C., Lundgren M., Macias J., Maganito S.C., Malundo A.F.G., Manrique R.D., Manzini P.M., Marcos M., Marquez I., Martinez-Marcos F.J., Mata A.M., McArthur C.J., McQuilten Z.K., McVerry B.J., Menon D.K., Meyfroidt G., Mirasol M.A.L., Misset B., Molton J.S., Mondragon A.V., Monsalve D.M., Moradi Choghakabodi P., Morpeth S.C., Mouncey P.R., Moutschen M., Muller-Tidow C., Murphy E., Najdovski T., Nichol A.D., Nielsen H., Novak R.M., O'Sullivan M.V.N., Olalla J., Osibogun A., Osikomaiya B., Oyonarte S., Pardo-Oviedo J.M., Patel M.C., Paterson D.L., Pena-Perez C.A., Perez-Calatayud A.A., Perez-Alba E., Perkina A., Perry N., Pouladzadeh M., Poyato I., Price D.J., Quero A.K.H., Rahman M.M., Rahman M.S., Ramesh M., Ramirez-Santana C., Rasmussen M., Rees M.A., Rego E., Roberts J.A., Roberts D.J., Rodriguez Y., Rodriguez-Bano J., Rogers B.A., Rojas M., Romero A., Rowan K.M., Saccona F., Safdarian M., Santos M.C.M., Sasadeusz J., Scozzari G., Shankar-Hari M., Sharma G., Snelling T., Soto A., Tagayuna P.Y., Tang A., Tatem G., Teofili L., Tong S.Y.C., Turgeon A.F., Veloso J.D., Venkatesh B., Ventura-Enriquez Y., Webb S.A., Wiese L., Wiken C., Wood E.M., Yusubalieva G.M., Zacharowski K., Zarychanski R., Khanna N., Moher D., Goodman S.N., Ioannidis J.P.A., and Hemkens L.G.

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). Method(s): 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. Result(s): 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

Published
2021

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

Author

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, Neto, AC, D'Antico, S, Daly, J, Danielle, F, Davis, JS, De Rosa, FG, Denholm, JT, Denkinger, CM, Desmecht, D, Diaz-Coronado, JC, Diaz 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, DT, Gaviria Garcia, PA, Giron-Gonzalez, J-A, Gomez-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, A, 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-Diaz, JM, Lopez-Robles, C, Lopez-Cardenas, S, Lopez-Plaza, I, Lucero, JAC, Lundgren, M, Macias, J, Maganito, SC, Malundo, AFG, Manrique, RD, Manzini, PM, Marcos, M, Marquez, I, Javier Martinez-Marcos, F, Mata, AM, McArthur, CJ, McQuilten, ZK, McVerry, BJ, Menon, DK, Meyfroidt, G, Mirasol, MAL, Misset, B, Molton, JS, Mondragon, A, Monsalve, DM, Choghakabodi, PM, Morpeth, SC, Mouncey, PR, Moutschen, M, Muller-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, Pena-Perez, CA, Perez-Calatayud, AA, Perez-Alba, E, Perkina, A, Perry, N, Pouladzadeh, M, Poyato, I, Price, DJ, Quero, AKH, Rahman, MM, Rahman, MS, Ramesh, M, Ramirez-Santana, C, Rasmussen, M, Rees, MA, Rego, E, Roberts, JA, Roberts, DJ, Rodriguez, Y, Rodriguez-Bano, 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, Wiken, C, Wood, EM, Yusubalieva, GM, Zacharowski, K, Zarychanski, R, Khanna, N, Moher, D, Goodman, SN, Ioannidis, JPA, Hemkens, LG, 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, Neto, AC, D'Antico, S, Daly, J, Danielle, F, Davis, JS, De Rosa, FG, Denholm, JT, Denkinger, CM, Desmecht, D, Diaz-Coronado, JC, Diaz 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, DT, Gaviria Garcia, PA, Giron-Gonzalez, J-A, Gomez-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, A, 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-Diaz, JM, Lopez-Robles, C, Lopez-Cardenas, S, Lopez-Plaza, I, Lucero, JAC, Lundgren, M, Macias, J, Maganito, SC, Malundo, AFG, Manrique, RD, Manzini, PM, Marcos, M, Marquez, I, Javier Martinez-Marcos, F, Mata, AM, McArthur, CJ, McQuilten, ZK, McVerry, BJ, Menon, DK, Meyfroidt, G, Mirasol, MAL, Misset, B, Molton, JS, Mondragon, A, Monsalve, DM, Choghakabodi, PM, Morpeth, SC, Mouncey, PR, Moutschen, M, Muller-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, Pena-Perez, CA, Perez-Calatayud, AA, Perez-Alba, E, Perkina, A, Perry, N, Pouladzadeh, M, Poyato, I, Price, DJ, Quero, AKH, Rahman, MM, Rahman, MS, Ramesh, M, Ramirez-Santana, C, Rasmussen, M, Rees, MA, Rego, E, Roberts, JA, Roberts, DJ, Rodriguez, Y, Rodriguez-Bano, 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, Wiken, C, Wood, EM, Yusubalieva, GM, Zacharowski, K, Zarychanski, R, Khanna, N, Moher, D, Goodman, SN, Ioannidis, JPA, and Hemkens, LG

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% o

Published
2021

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

Author

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 Angelo 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 Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U.H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, 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 Mae 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 Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, 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 Anne 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 Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina 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 Kristine 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 Clariza 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., 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 Angelo 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 Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U.H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, 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 Mae 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 Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, 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 Anne 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 Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina 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 Kristine 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 Clariza 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., and Hemkens, Lars G.

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 evi

Published
2021

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

Author

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., Aomar, I. F., Argumanis, L. E., Averyanov, A., Baklaushev, V. P., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L. B., Bowen, A. C., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D. H., Cardesa, A., Carnate, J. M., Castillo, G. J. J., Cavallo, R., Chowdhury, F. R., Chowdhury, F. U. H., Ciccone, G., Cingolani, Antonella, Climacosa, F. M. M., Compernolle, V., Cortez, C. F. N., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J. S., De Rosa, F. G., Denholm, J. T., Denkinger, C. M., Desmecht, D., Diaz-Coronado, J. C., Diaz Ponce-Medrano, J. A., Donneau, A. -F., Dumagay, T. E., Dunachie, S., Dungog, C. C., Erinoso, O., Escasa, I. M. S., Estcourt, L. J., Evans, A., Evasan, A. L. M., Fareli, C. J., Fernandez-Sanchez, V., Galassi, C., Gallo, J. E., Garcia, P. J., Garcia, P. L., Garcia, J. A., Garigliany, M., Garza-Gonzalez, E., Gauiran, D. T. V., Gaviria Garcia, P. A., Giron-Gonzalez, J. -A., Gomez-Almaguer, D., Gordon, A. C., Gothot, A., Grass Guaqueta, J. S., Green, C., Grimaldi, D., Hammond, N. E., Harvala, H., Heralde, F. M., Herrick, J., Higgins, A. M., Hills, T. E., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J. M., Ivanov, A. V., Janssen, M., Jennings, J. H., Jha, V., King, R. A. N., 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-Diaz, J. M., Lopez-Robles, C., Lopez-Cardenas, S., Lopez-Plaza, I., Lucero, J. A. C., Lundgren, M., Macias, J., Maganito, S. C., Malundo, A. F. G., Manrique, R. D., Manzini, P. M., Marcos, M., Marquez, I., Martinez-Marcos, F. J., Mata, A. M., Mcarthur, C. J., Mcquilten, Z. K., Mcverry, B. J., Menon, D. K., Meyfroidt, G., Mirasol, M. A. L., Misset, B., Molton, J. S., Mondragon, A. V., Monsalve, D. M., Moradi Choghakabodi, P., Morpeth, S. C., Mouncey, P. R., Moutschen, M., Muller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A. D., Nielsen, H., Novak, R. M., O'Sullivan, M. V. N., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J. M., Patel, M. C., Paterson, D. L., Pena-Perez, C. A., Perez-Calatayud, A. A., Perez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D. J., Quero, A. K. H., Rahman, M. M., Rahman, M. S., Ramesh, M., Ramirez-Santana, C., Rasmussen, M., Rees, M. A., Rego, E., Roberts, J. A., Roberts, D. J., Rodriguez, Y., Rodriguez-Bano, J., Rogers, B. A., Rojas, M., Romero, A., Rowan, K. M., Saccona, F., Safdarian, M., Santos, M. C. M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P. Y., Tang, A., Tatem, G., Teofili, Luciana, Tong, S. Y. C., Turgeon, A. F., Veloso, J. D., Venkatesh, B., Ventura-Enriquez, Y., Webb, S. A., Wiese, L., Wiken, C., Wood, E. M., Yusubalieva, G. M., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S. N., Ioannidis, J. P. A., Hemkens, L. G., Cingolani A. (ORCID:0000-0002-3793-2755), Teofili L. (ORCID:0000-0002-7214-1561), 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., Aomar, I. F., Argumanis, L. E., Averyanov, A., Baklaushev, V. P., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L. B., Bowen, A. C., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D. H., Cardesa, A., Carnate, J. M., Castillo, G. J. J., Cavallo, R., Chowdhury, F. R., Chowdhury, F. U. H., Ciccone, G., Cingolani, Antonella, Climacosa, F. M. M., Compernolle, V., Cortez, C. F. N., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J. S., De Rosa, F. G., Denholm, J. T., Denkinger, C. M., Desmecht, D., Diaz-Coronado, J. C., Diaz Ponce-Medrano, J. A., Donneau, A. -F., Dumagay, T. E., Dunachie, S., Dungog, C. C., Erinoso, O., Escasa, I. M. S., Estcourt, L. J., Evans, A., Evasan, A. L. M., Fareli, C. J., Fernandez-Sanchez, V., Galassi, C., Gallo, J. E., Garcia, P. J., Garcia, P. L., Garcia, J. A., Garigliany, M., Garza-Gonzalez, E., Gauiran, D. T. V., Gaviria Garcia, P. A., Giron-Gonzalez, J. -A., Gomez-Almaguer, D., Gordon, A. C., Gothot, A., Grass Guaqueta, J. S., Green, C., Grimaldi, D., Hammond, N. E., Harvala, H., Heralde, F. M., Herrick, J., Higgins, A. M., Hills, T. E., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J. M., Ivanov, A. V., Janssen, M., Jennings, J. H., Jha, V., King, R. A. N., 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-Diaz, J. M., Lopez-Robles, C., Lopez-Cardenas, S., Lopez-Plaza, I., Lucero, J. A. C., Lundgren, M., Macias, J., Maganito, S. C., Malundo, A. F. G., Manrique, R. D., Manzini, P. M., Marcos, M., Marquez, I., Martinez-Marcos, F. J., Mata, A. M., Mcarthur, C. J., Mcquilten, Z. K., Mcverry, B. J., Menon, D. K., Meyfroidt, G., Mirasol, M. A. L., Misset, B., Molton, J. S., Mondragon, A. V., Monsalve, D. M., Moradi Choghakabodi, P., Morpeth, S. C., Mouncey, P. R., Moutschen, M., Muller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A. D., Nielsen, H., Novak, R. M., O'Sullivan, M. V. N., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J. M., Patel, M. C., Paterson, D. L., Pena-Perez, C. A., Perez-Calatayud, A. A., Perez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D. J., Quero, A. K. H., Rahman, M. M., Rahman, M. S., Ramesh, M., Ramirez-Santana, C., Rasmussen, M., Rees, M. A., Rego, E., Roberts, J. A., Roberts, D. J., Rodriguez, Y., Rodriguez-Bano, J., Rogers, B. A., Rojas, M., Romero, A., Rowan, K. M., Saccona, F., Safdarian, M., Santos, M. C. M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P. Y., Tang, A., Tatem, G., Teofili, Luciana, Tong, S. Y. C., Turgeon, A. F., Veloso, J. D., Venkatesh, B., Ventura-Enriquez, Y., Webb, S. A., Wiese, L., Wiken, C., Wood, E. M., Yusubalieva, G. M., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S. N., Ioannidis, J. P. A., Hemkens, L. G., Cingolani A. (ORCID:0000-0002-3793-2755), and Teofili L. (ORCID:0000-0002-7214-1561)

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

Published
2021

15. Diagnostic laparoscopy to exclude malrotation following inconclusive upper gastrointestinal contrast study in infants

Author

Nigel J. Hall, A Alzamrooni, K Sloan, Francesca Stedman, and Ori Ron

Subjects
Male, Radiography, Abdominal, medicine.medical_specialty, medicine.medical_treatment, Contrast Media, Diagnostic laparoscopy, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Laparotomy, Pediatric surgery, Intestine, Small, Medicine, Upper gastrointestinal, Humans, Laparoscopy, Ultrasonography, medicine.diagnostic_test, business.industry, Infant, Newborn, General Medicine, medicine.disease, Volvulus, Intestinal malrotation, Pediatrics, Perinatology and Child Health, 030211 gastroenterology & hepatology, Surgery, Female, Radiology, business, Complication, Intestinal Volvulus
Abstract

Purpose: We report the use of diagnostic laparoscopy as an alternative to laparotomy in the investigation of infants with clinical features concerning for malrotation and inconclusive upper gastrointestinal contrast study. Method: Case note review of all infants in whom laparoscopy was performed during 2016–2020 to investigate for possible malrotation. Results: Eight infants were identified. All presented with acute clinical features of malrotation (bilious vomit) without evidence of an alternate explanatory diagnosis. All underwent upper gastrointestinal contrast study, with three also undergoing abdominal ultrasound. The radiological examinations could not exclude malrotation and all proceeded to laparoscopy. At laparoscopy, the small intestine was run to exclude the presence of midgut volvulus. In six cases, normal rotation was confirmed and no abnormal pathology was found. Two proceeded to laparotomy and underwent correction of malrotation. All infants recovered without complication. Conclusion: Laparoscopy is an excellent modality for further investigation of infants presenting acutely in whom intestinal malrotation cannot be formally excluded radiologically. The positive identification of the DJ flexure and cecum in correct anatomical sites, both fixed to the posterior abdominal wall, provides adequate reassurance of low risk of volvulus and avoids a full laparotomy. We recommend diagnostic laparoscopy in cases of inconclusive upper gastrointestinal contrast study.

Published
2020

16. Cardiac competence of the paraxial head mesoderm fades concomitant with a shift towards the head skeletal muscle programme

Author

Afnan Alzamrooni, Petra Mendes Vieira, Nicoletta Murciano, Matthew Wolton, Frank R. Schubert, Samuel C. Robson, and Susanne Dietrich

Subjects
Skull, Head mesoderm, animal structures, medicine.anatomical_structure, Smooth muscle, Head (linguistics), embryonic structures, medicine, Skeletal muscle, Embryo, Biology, Cell biology
Abstract

The vertebrate head mesoderm provides the heart, the great vessels, some smooth and most head skeletal muscle, in addition to parts of the skull. It has been speculated that the ability to generate cardiac and smooth muscle is the evolutionary ground-state of the tissue. However, whether indeed the entire head mesoderm has generic cardiac competence, how long this may last, and what happens as cardiac competence fades, is not clear.Bone morphogenetic proteins (Bmps) are known to promote cardiogenesis. Using 41 different marker genes in the chicken embryo, we show that the paraxial head mesoderm that normally does not engage in cardiogenesis has the ability to respond to Bmp for a long time. However, Bmp signals are interpreted differently at different time points. Up to early head fold stages, the paraxial head mesoderm is able to read Bmps as signal to engage in the cardiac programme; the ability to upregulate smooth muscle markers is retained slightly longer. Notably, as cardiac competence fades, Bmp promotes the head skeletal muscle programme instead. The switch from cardiac to skeletal muscle competence is Wnt-independent as Wnt caudalises the head mesoderm and also suppresses Msc-inducing Bmp provided by the prechordal plate, thus suppressing both the cardiac and the head skeletal muscle programmes.Our study for the first time suggests a specific transition state in the embryo when cardiac competence is replaced by skeletal muscle competence. It sets the stage to unravel the cardiac-skeletal muscle antagonism that is known to partially collapse in heart failure.Summary statementThe head mesoderm has generic cardiac competence until early head fold stages. Thereafter, cardiac competence fades in the paraxial region, and Bmp promotes head skeletal muscle programmes instead of cardiac programmes.

Published
2019
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18. Additional file 6 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 6. Funnel plot.

19. Additional file 4 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 4. Identified potentially eligible trials not included in the analysis.

20. Additional file 1 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
Data_FILES, 3. Good health
Abstract

Additional file 1. Search strategy.

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

Author

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 Angelo 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 Jr J, Cavallo, Rossana, Chowdhury, Fazle R, Chowdhury, Forhad UH, Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M, Compernolle, Veerle, Cortez, Carlo Francisco N, Costa Neto, Abel, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S, De Rosa, Francesco Giuseppe, 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 Mae S, Estcourt, Lise J, Evans, Amy, Evasan, Agnes LM, 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 Thaddeus V, Gaviria García, Paula A, Giron-Gonzalez, Jose-Antonio, Gómez-Almaguer, David, Gordon, Anthony C, Gothot, André, Grass Guaqueta, Jeser Santiago, 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 Anne 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 Anne C, Lundgren, Maria, Macías, Juan, Maganito, Sandy C, Malundo, Anna Flor G, Manrique, Rubén D, Manzini, Paola M, Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M, McArthur, Colin J, McQuilten, Zoe K, McVerry, Bryan J, Menon, David K, Meyfroidt, Geert, Mirasol, Ma Angelina 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 VN, 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 Kristine 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 Clariza 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 YC, 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 PA, and Hemkens, Lars G

Subjects
Meta-analysis, Convalescent plasma, Treatment Outcome, SARS-CoV-2, Immunization, Passive, COVID-19, Humans, COVID-19 Serotherapy, 3. Good health, Randomized Controlled Trials as Topic
Abstract

Funder: laura and john arnold foundation, 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.

22. Additional file 5 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 5. Risk of bias.

23. Additional file 6 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 6. Funnel plot.

24. Additional file 5 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 5. Risk of bias.

25. Additional file 2 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
TheoryofComputation_MISCELLANEOUS, InformationSystems_INFORMATIONSYSTEMSAPPLICATIONS, Data_FILES, GeneralLiterature_MISCELLANEOUS, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract

Additional file 2. Email invitation.

26. Additional file 7 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 7. Sensitivity analyses: various meta-analytic approaches.

27. Additional file 4 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 4. Identified potentially eligible trials not included in the analysis.

28. Additional file 3 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
GeneralLiterature_INTRODUCTORYANDSURVEY, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Data_FILES, ComputingMilieux_LEGALASPECTSOFCOMPUTING, 3. Good health
Abstract

Additional file 3. Amendments to the protocol.

29. Additional file 2 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
TheoryofComputation_MISCELLANEOUS, InformationSystems_INFORMATIONSYSTEMSAPPLICATIONS, Data_FILES, GeneralLiterature_MISCELLANEOUS, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract

Additional file 2. Email invitation.

30. Additional file 7 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
3. Good health
Abstract

Additional file 7. Sensitivity analyses: various meta-analytic approaches.

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

Author

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 Angelo 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 Jr J, Cavallo, Rossana, Chowdhury, Fazle R, Chowdhury, Forhad UH, Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M, Compernolle, Veerle, Cortez, Carlo Francisco N, Costa Neto, Abel, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S, De Rosa, Francesco Giuseppe, Denholm, Justin T, Denkinger, Claudia M, Desmecht, Daniel, D��az-Coronado, Juan C, D��az Ponce-Medrano, Juan A, Donneau, Anne-Fran��oise, Dumagay, Teresita E, Dunachie, Susanna, Dungog, Cecile C, Erinoso, Olufemi, Escasa, Ivy Mae S, Estcourt, Lise J, Evans, Amy, Evasan, Agnes LM, 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 Thaddeus V, Gaviria Garc��a, Paula A, Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C, Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N, Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M, L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C, Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C, Malundo, Anna Flor G, Manrique, Rub��n D, Manzini, Paola M, Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M, McArthur, Colin J, McQuilten, Zoe K, McVerry, Bryan J, Menon, David K, Meyfroidt, Geert, Mirasol, Ma Angelina L, Misset, Beno��t, Molton, James S, Mondragon, Alric V, Monsalve, Diana M, Moradi Choghakabodi, Parastoo, Morpeth, Susan C, Mouncey, Paul R, Moutschen, Michel, M��ller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D, Nielsen, Henrik, Novak, Richard M, O'Sullivan, Matthew VN, Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M, Patel, Mahesh C, Paterson, David L, Pe��a-Perez, Carlos A, Perez-Calatayud, Angel A, P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J, Quero, Anne Kristine H, Rahman, Md M, Rahman, Md S, Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A, Rego, Eduardo, Roberts, Jason A, Roberts, David J, Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A, Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M, Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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 YC, Turgeon, Alexis F, Veloso, Januario D, Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A, Wiese, Lothar, Wik��n, Christian, Wood, Erica M, Yusubalieva, Gaukhar M, Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N, Ioannidis, John PA, and Hemkens, Lars G

Subjects
Meta-analysis, Convalescent plasma, SARS-CoV-2, COVID-19, 3. Good health, Research Article
Abstract

Funder: laura and john arnold foundation; doi: http://dx.doi.org/10.13039/100009827, 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.

32. Additional file 3 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

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 Angelo 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 Jr. J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D���Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, D��az-Coronado, Juan C., D��az Ponce-Medrano, Juan A., Donneau, Anne-Fran��oise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae 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 Thaddeus V., Gaviria Garc��a, Paula A., Giron-Gonzalez, Jose-Antonio, G��mez-Almaguer, David, Gordon, Anthony C., Gothot, Andr��, Grass Guaqueta, Jeser Santiago, 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 Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Fran��ois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-D��az, Jorge M., L��pez-Robles, Concepci��n, L��pez-C��rdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Mac��as, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rub��n D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Mart��nez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma. Angelina L., Misset, Beno��t, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, M��ller-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., Pe��a-Perez, Carlos A., Perez-Calatayud, Angel A., P��rez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md. M., Rahman, Md. S., Ramesh, Mayur, Ram��rez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodr��guez, Yhojan, Rodr��guez-Ba��o, Jes��s, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza 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, Wik��n, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.

Subjects
GeneralLiterature_INTRODUCTORYANDSURVEY, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Data_FILES, ComputingMilieux_LEGALASPECTSOFCOMPUTING, 3. Good health
Abstract

Additional file 3. Amendments to the protocol.

33. Inherent Metabolic Adaptations in Adult Spiny Mouse ( Acomys ) Cardiomyocytes Facilitate Enhanced Cardiac Recovery Following Myocardial Infarction.

Author

Kuppa A, Alzamrooni A, Lopez R, Suhan T, Chaudhary R, Collins N, Van den Bergh F, Abouleisa R, Wang H, Mohamed T, Satin J, Lyssiotis C, Beard DA, and Abdel-Latif A

Abstract

The adult mammalian heart has limited regenerative capacity following injury, leading to progressive heart failure and mortality. Recent studies have identified the spiny mouse ( Acomys ) as a unique model for mammalian cardiac isch3emic resilience, exhibiting enhanced recovery after myocardial infarction (MI) compared to commonly used laboratory mouse strains. However, the underlying cellular and molecular mechanisms behind this unique response remain poorly understood. In this study, we comprehensively characterized the metabolic characteristics of cardiomyocytes in Acomys compared to the non-regenerative Mus musculus . We utilized single-nucleus RNA sequencing (snRNA-seq) in sham-operated animals and 1, 3, and 7 days post-myocardial infarction to investigate cardiomyocytes' transcriptomic and metabolomic profiles in response to myocardial infarction. Complementary targeted metabolomics, stable isotope-resolved metabolomics, and functional mitochondrial assays were performed on heart tissues from both species to validate the transcriptomic findings and elucidate the metabolic adaptations in cardiomyocytes following ischemic injury. Transcriptomic analysis revealed that Acomys cardiomyocytes inherently upregulate genes associated with glycolysis, the pentose phosphate pathway, and glutathione metabolism while downregulating genes involved in oxidative phosphorylation (OXPHOS). These metabolic characteristics are linked to decreased reactive oxygen species (ROS) production and increased antioxidant capacity. Our targeted metabolomic studies in heart tissue corroborated these findings, showing a shift from fatty acid oxidation to glycolysis and ancillary biosynthetic pathways in Acomys at baseline with adaptive changes post-MI. Functional mitochondrial studies indicated a higher reliance on glycolysis in Acomys compared to Mus , underscoring the unique metabolic phenotype of Acomys hearts. Stable isotope tracing experiments confirmed a shift in glucose utilization from oxidative phosphorylation in Acomys . In conclusion, our study identifies unique metabolic characteristics of Acomys cardiomyocytes that contribute to their enhanced ischemic resilience following myocardial infarction. These findings provide novel insights into the role of metabolism in regulating cardiac repair in adult mammals. Our work highlights the importance of inherent and adaptive metabolic flexibility in determining cardiomyocyte ischemic responses and establishes Acomys as a valuable model for studying cardiac ischemic resilience in adult mammals.

Published
2024
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