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Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial
Philippe Bégin, Jeannie Callum, Erin Jamula, Richard J. Cook, Nancy M. Heddle, Alan Tinmouth, Michelle P. Zeller, Guillaume Beaudoin-Bussières, Luiz Amorim, Renée Bazin, Kent Cadogan Loftsgard, Richard Carl, Michaël Chassé, Melissa M. Cushing, Nick Daneman, Dana V. Devine, Jeannot Dumaresq, Dean Fergusson, Caroline Gabe, Marshall J. Glesby, Na Li, Yang Liu, Allison McGeer, Nancy Robitaille, Bruce S. Sachais, Damon C. Scales, Lisa Schwartz, Nadine Shehata, Alexis F. Turgeon, Heidi Wood, Ryan Zarychanski, Andrés Finzi, Danièle Marceau, Andy Huang, Holly Carr, Yulia Lin, Rosemarie Lall, Christopher J Graham, Christine Arsenault, Valérie Sales, Davinder Sidhu, Makeda Semret, Caroline Hamm, Eneko Arhanchiague, Ziad Solh, Nadim Srour, Karim Soliman, Colin Yee, Vinçent Laroche, Susan Nahirniak, Christina Greenaway, Menaka Pai, Andréanne Côté, Jennifer Tsang, Christine Cserti‐Gazdewich, Danielle Talbot, Sébastien Poulin, Rodrigo Régnier Chemim Guimarães, Moira Rushton-Marovac, Alexandra Langlois, Shuoyan Ning, Andrew W. Shih, Mélissa Boileau, Harjot Singh, Donna Ledingham, Arjuna Ponnampalam, Matthew Yan, Oksana Prokopchuk‐Gauk, André Poirier, Gabriel Girouard, Olivier Drouin, David Harris, Madéleine Durand, Emily Rimmer, Daniel Ovakim, François Ménard, Glenna Cuccarolo, Julie Carruthers, Kayla J. Lucier, Valérie Arsenault, Marie‐Christine Auclair, Meda Avram, Michael Brassard, Sabrina Cerro, Verónica González Martínez, Julie Morin, Marie Saint-Jacques, Maxime Veillette, Chantal Armali, Amie Kron, Dimpy Modi, Joanne Duncan, Pauline Justumus, Melanie St John, Geneviève St‐Onge, Milena Hadzi‐Tosev, Pierre‐Marc Dion, Lawrence McGillivary, Andre Valleteau de Moulliac, Sheila A. Nyman, Stephanie Perilli, Paulette Jean Van Vliet, Shannon Lane, Rebecca Pereira, Emily Sirotich, Julie Abelson, Saara Greene, Aditi Khandelwal, Swarni Thakar, Sarah Longo, Sai Priya Anand, Mehdi Benlarbi, Catherine Bourassa, Marianne Boutin, Jade Descôteaux-Dinelle, Gabrielle Gendron‐Lepage, Guillaume Goyette, Annemarie Laumaea, Halima Medjahed, Jérémie Prévost, Jonathan Richard, Daniel E. Kaufmann, Elsa Brunet‐Ratnasingham, Nicolas Chaumont, Michael Drebot, Alyssia Robinson, Emelissa J. Mendoza, Kristina Dimitrova, Kathy Manguiat, Clark Phillipson, Michael Chan, David T. Evans, Yi-Chan Lin, Lucie Boyer, Marc Cloutier, Mathieu Drouin, Éric Ducas, Nathalie Dussault, Marie‐Josée Fournier, Patricia Landy, Marie-Ève Nolin, Josée Perreault, Tony Tremblay, Ishac Nazy, Feng Xie, David Liu, Michelle Wong, Gus Silverio, Kristin Walkus, Mikaela Barton, Katherine Haveman, Darlene Mueller, Ashley Scott, Matthew Moher, Gordon Wood, Tracey Roarty, F. C. Auld, Gayle Carney, Virginia Thomson, Rodrigo Onell, Keith R. Walley, Katie Donohoe, Crystal Brunk, Geraldine Hernández, Tina Jacobucci, Lynda Lazosky, Puneet Mann, Geeta Raval, Ligia Araujo Zampieri, Mypinder S. Sekhon, Alissa Wright, Nicola James, Gaby Chang, Roy Chen, Kanwal Deol, Jorell Gantioqui, Elyse Larsen, Namita Ramdin, Margaret Roche, Kristin Rosinski, Lawrence Sham, Michelle Storms, Mark R. Gillrie, Etienne Mahé, Deepa Suryanarayan, Alejandra Ugarte-Torres, Traci Robinson, Mitchell Gibbs, Julia Hews‐Girard, Marnie Holmes, Joanna McCarthy, Meagan Ody, Karen Doucette, Wendy Sligl, Ashlesha Sonpar, K Robertson, Jeffrey Narayan, Leka Ravindran, Breanne Stewart, Lori Zapernick, Stephen Lee, Eric Sy, Alexander Wong, Karolina Gryzb, Sarah Craddock, Dennaye Fuchs, Danielle Myrah, Sana Sunny, Sheila Rutledge Harding, Siddarth Kogilwaimath, Nancy Hodgson, Dawn Johnson, Simona Meier, Kim Thomson, Amila Heendeniya, Brett L. Houston, Yoav Kenyan, Sylvain Lother, Kendiss Olafson, Barret Rush, Terence Wuerz, Dayna Solvason, Lisa Albensi, Soumya Alias, Nora Choi, Laura M. Curtis, Maureen Hutmacher, Hessam H. Kashani, Debra Lane, Nicole Marten, Tracey Pronyk-Ward, Lisa Rigaux, Rhonda Silva, Quinn Tays, Renuka Naidu, Jane Mathews, Margaret Mai, Victoria Miceli, Liz Molson, Linda Schaefer, Michel Ferreira Cardia Haddad, Shannon Landry, Robert Chernish, Rebecca Kruisselbrink, Theresa Liu, Jayna Jeromin, Atif Siddiqui, Carla Girolametto, Kristin Krokoszynski, Cheryl Main, Alison Fox‐Robichaud, Bram Rochwerg, Erjona Kruja, Dana Ellingham, Disha Sampat, Ngan Tang, Daniela Leto, Meera Karunakaran, Daniel Ricciuto, Kelly Fusco, Taneera Ghate, Holly Robinson, Ian Ball, Sarah Shalhoub, Marat Slessarev, Michael G. Silverman, Eni Nano, Tracey Bentall, Eileen Campbell, Jeffery Kinney, Seema Nair Parvathy, Evridiki Fera, Anthony La Delfa, Jeya Nadarajah, H. Solow, Edeliza Mendoza, Katrina Engel, Diana Monaco, Laura Kononow, Sutharsan Suntharalingam, Mike Fralick, Laveena Munshi, Samia Saeed, Elaine Hsu, Karim Ali, Erick Duan, George Farjou, Lorraine Jenson, Mary Salib, Lisa Patterson, Swati Anant, Josephine Ding, Jane Jomy, Pavani Das, Anna Geagea, Sarah Ingber, Elliot Owen, Alexandra Lostun, Tashea Albano, Antara Chatterjee, Manuel Giraldo, Jennifer Hickey, Ida Lee, Nicholas Pasquale, Mary Rahmat, Leonita Aguiar, Ashmina Damani, Suhyoung Hong, Mona Kokabi, Carolyn Perkins, Juthaporn Cowan, Tony Giulivi, Derek R. MacFadden, Joe Cyr, Amanda Pecarskie, Rebecca Porteous, Priscila Ogawa Vedder, Irene Watpool, Phil Berardi, Laith Bustani, Alison Graver, Akshai Iyengar, Magdalena Kisilewicz, Jake Majewski, Misha Marovac, Ruchi Murthy, Karan Sharma, Marina Walcer, Zain Chagla, Jason Pui Yin Cheung, France Clarke, Karlo Matic, Travis Carpenter, Kevin L. Schwartz, Paril Suthar, Aziz Jiwajee, Daniel Lindsay, Aftab Malik, Brandon Tse, Larissa Matukas, Joel G. Ray, Shirley K. Bell, Elizabeth Krok, Ray Guo, Susan John, Vishal D. Joshi, Jessica Keen, Chris Lazongas, Jacqueline Ostro, Kevin Shore, Jianmin Wang, JinCheol Choi, Pujitha Nallapati, Tina Irwin, Victor Wang, Petra Sheldrake, Neill K. J. Adhikari, Hannah Wunsch, Jacob Bailey, Harley Meirovich, Connie Colavecchia, Eiad Kahwash, Sachin Sud, Martin Romano, Bryan Coburn, Lorenzo Del Sorbo, John Granton, Shahid Husain, Jacob Pendergrast, Abdu Sharkawy, Liz Wilcox, Maria Kulikova, Sophia Z. Massin, Wendy Kennette, Ian Mazzetti, Krista Naccarato, Grace Park, Alex Pennetti, Corrin Primeau, Cathy Vilag, Yves Lapointe, Anne‐Sophie Lemay, Emmanuelle Duceppe, Benjamin Rioux‐Massé, Cécile Tremblay, Pascale Arlotto, Claudia Bouchard, Stephanie Matte, Marc Messier-Peet, Charles-Langis Francoeur, François Lauzier, Guillaume Leblanc, David Bellemare, Ève Cloutier, Olivier Costerousse, Émilie Couillard Chénard, Rana Daher, Marjorie Daigle, Stéphanie Grenier, Gabrielle Guilbeault, Marie-Pier Rioux, Maude St‐Onge, Antoine Tremblay, Brian Beaudoin, L. Lanthier, Pierre Larrivée, Pierre‐Aurèle Morin, Élaine Carbonneau, Robert Lacasse, Julie Autmizguine, Isabelle Boucoiran, Geneviève Du Pont‐Thibodeau, Annie La Haye, Vincent Lague, Karine Léveillé, Caroline Quach-Thanh, Guillaume Émériaud, Philippe Jouvet, Élie Haddad, Camille Turgeon-Provost, Susan M. Fox, Diaraye Baldé, Lorraine Ménard, Suzanne Morissette, Miriam Schnorr-Meloche, Andrée-Anne Turcotte, Caroline Vallée, Stéphanie Castonguay, Tuyen Nguyen, Natalie Rivest, Marios Roussos, Esther Simoneau, Andreea Belecciu, Marie-Hélène Bouchard, Eric Daviau, Cynthia L. Martin, Nicole Sabourin, Solange Tremblay, Émilie Gagné, Nancy-Lisa Gagné, Julie Larouche, Vanessa Larouche, Véronick Tremblay, Vicky Tremblay, Pierre Blanchette, David Claveau, Marianne Lamarre, Danielle Tapps, Martin Albert, Anatolie Duca, Jean‐Michel Leduc, Jean-Samuel Boudreault-Pedneault, Annie Barsalou, Suzanne Deschênes-Dion, Stéphanie Ibrahim, Stéphanie Ridyard, Julie Rousseau, Stéphane P. Ahern, Marie-Pier Arsenault, Simon-Frédéric Dufresne, Luigina Mollica, Hang Ting Wang, Soizic Beau, Dominique Beaupré, Marjolaine Dégarie, Iris Delorme, Melissa Farkas, Michel‐Olivier Gratton, Arnaud Guertin, Guylaine Jalbert, Mélanie Meilleur, Charles Ratté Labrecque, Elaine Vieira Santos, Jason Lu, Julien Auger, Marie-Claude Lessard, Louay Mardini, Yves Pesant, Laurie Delves, Lisa Delves, Sophie Denault, С. Ю. Григорова, Michelle Lambert, Nathalie Langille, Corinne Langlois, Caroline Rock, Yannick Sardin-Laframboise, Patrick Archambault, Joannie Bélanger-Pelletier, Estel Duquet-Deblois, Vanessa Dupuis-Picard, Yannick Hamelin, Samuel Leduc, Mélanie N. Richard, Marc Fortin, Philippe Gervais, Marie‐Ève Boulay, Claudine Ferland, Jakie Guertin, Johane Lepage, Annie Roy, Sarit Assouline, Stephen Caplan, Ling Yuan Kong, Christina Canticas, Carley Mayhew, Johanne Ouedraogo, Tévy-Suzy Tep, Gerald Batist, Matthew P. Cheng, Marina B. Klein, Nadine Kronfli, Patricia Pelletier, Salman Qureshi, Donald C. Vinh, Robert Dziarmaga, Hansi Peiris, Karène Proulx‐Boucher, Jonathan Roger, Molly-Ann Rothschild, Chung-Yan Yuen, Sapha Barkati, Jean‐Pierre Routy, Sondra Sinanan-Pelletier, Rémi LeBlanc, Ève St‐Hilaire, Patrick Thibeault, Karine Morin, Gilberte Caissie, Jackie Caissie Collette, L. Daigle, Mélissa Daigle, Bianca Gendron, Nathalie Godin, Angela Lapointe, G. Moreau, Lola Ouellette-Bernier, Joanne Rockburn, Brigitte Sonier-Ferguson, Christine M. Wilson, Robert A. DeSimone, Grant Ellsworth, Rebecca C. Fry, Noah Goss, Roy M. Gulick, Carlos Vaamonde, Timothy Wilkin, Celine Arar, Jonathan Berardi, Dennis Chen, Cristina Garcia-Miller, Arthur Goldbach, Lauren Gripp, Danielle Hayden, Kathleen Kane, Jiamin Li, Kinge-Ann Marcelin, Christina Megill, Meredith Nelson, Ailema Paguntalan, Gabriel Raab, Gianna Resso, Roxanne Rosario, Noah Rossen, Shoran Tamura, Ethan Zhao, Cheryl Goss, Eshan U. Patel, Sonal Paul, Tiffany Romero, Naima ElBadri, Lina Flores, Tricia Sandoval, Shashi N. Kapadia, Ljiljana V. Vasović, Shanna-Kay Griffiths, Daniel Alvarado, Fiona Goudy, Melissa Lewis, Marina Loizou, Rita Louie, Chantale Pambrun, Sylvia Torrance, Steven J. Drews, Janet McManus, Oriela Cuevas, Wanda Lafresne, Patrizia Ruoso, Christine Shin, Tony Steed, Rachel N. Ward, Isabelle Allard, Marc Germain, Sébastien Girard, Éric Parent, Claudia-Mireille Pigeon, Maria Esther Lopes, Margarida Pêcego, Natalia Fonseca do Rosário, Carlos Alexandre da Costa Silva, Thais da Costa Oliveira, Maria Cristina Lopes, Sheila de Oliveira Garcia Mateos, Lucette Hall, Sarai Paradiso, D Strauss
Bibliographic record
VenueNature Medicine · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsMcMaster University Medical CentreJuravinski HospitalRoyal University HospitalAbbotsford Veterinary ClinicVitalité Health NetworkHôpital Maisonneuve-RosemontVancouver General HospitalQueensway-Carleton HospitalCanadian Blood ServicesInstitut universitaire de cardiologie et de pneumologie de QuébecGrand River HospitalLakeridge HealthCentre Intégré de Santé et de Services Sociaux des LaurentidesSt. Paul's HospitalCentre Hospitalier Universitaire de SherbrookeNiagara Health SystemJewish General HospitalHôpital Charles-Le MoyneRoyal Jubilee HospitalMount Sinai HospitalLondon Health Sciences CentreNorth York General HospitalMcGill University Health CentreWindsor Regional HospitalTrillium Health CentreHamilton General HospitalVictoria General HospitalUniversity Health NetworkSt Joseph's Health CentreUniversity of TorontoUniversity of AlbertaRockyview General HospitalUniversity of ManitobaCegep de Saint JeromeOttawa HospitalImpactUniversity of WaterlooUniversity of British ColumbiaSinai Health SystemRegina General HospitalSt. Joseph’s Healthcare HamiltonHealth Sciences CentreUniversity of CalgaryRoyal Alexandra HospitalMarkham Stouffville HospitalHôpital du Sacré-Cœur de MontréalMcMaster UniversityCentre intégré de santé et de services sociaux de Chaudière-AppalachesHéma-QuébecUniversité de MontréalCentre Hospitalier Universitaire Sainte-JustinePublic Health Agency of CanadaKingston Health Sciences CentreSt. Boniface HospitalBausch Health (Canada)University of OttawaSunnybrook Health Science CentreThe Scarborough HospitalPublic Health OntarioCentre Hospitalier de l’Université de MontréalQueen's UniversityUniversité Laval
FundersFonds de Recherche du Québec - SantéNational Institute of Environmental Health SciencesCanadian Institutes of Health ResearchUniversity of TorontoUniversity of AlbertaAlberta Health ServicesMcMaster UniversityMinistry of Health, SaskatchewanHealth Sciences Centre FoundationGovernment of CanadaFondation du CHUM
KeywordsMedicineRandomized controlled trialConfidence intervalOdds ratioInternal medicineRelative riskConvalescent plasmaAdverse effectIntubationCoronavirus disease 2019 (COVID-19)AnesthesiaDisease
Abstract
The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.031
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.246
Threshold uncertainty score1.000
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.031 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.034
GPT teacher head0.391
Teacher spread0.357 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
Study designRandomized trial
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations275
Published2021
Admission routes2
Has abstractyes