Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial
Authors: Philippe Bégin, Jeannie Callum, Erin Jamula, Richard 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 A. 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 Graham, Christine Arsenault, Valerie Sales, Davinder Sidhu, Makeda Semret, Caroline Hamm, Eneko Arhanchiague, Ziad Solh, Nadim Srour, Karim Soliman, Colin Yee, Vincent Laroche, Susan Nahirniak, Christina Greenaway, Menaka Pai, Andréanne Côté, Jennifer L. Y. Tsang, Christine Cserti-Gazdewich, Danielle Talbot, Sébastien Poulin, Rodrigo Guimaraes, Moira Rushton-Marovac, Alexandra Langlois, Shuoyan Ning, Andrew Shih, Mélissa Boileau, Harjot Singh, Donna Ledingham, Arjuna Ponnampalam, Matthew Yan, Oksana Prokopchuk-Gauk, André Poirier, Gabriel Girouard, Katerina Pavenski, Olivier Drouin, David Harris, Madeleine Durand, Emily Rimmer, Daniel Ovakim, François Ménard, Glenna Cuccarolo, Julie Carruthers, Kayla Lucier, Valérie Arsenault, Marie-Christine Auclair, Meda Avram, Michael Brassard, Sabrina Cerro, Véronica Martinez, 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, Katerina Pavenski, 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 Kaufmann, Elsa Brunet-Ratnasingham, Nicolas Chaumont, Michael Drebot, Alyssia Robinson, Emelissa Mendoza, Kristina Dimitrova, Kathy Manguiat, Clark Phillipson, Michael Chan, David Evans, James 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, Fiona Auld, Gayle Carney, Virginia Thomson, Rodrigo Onell, Keith Walley, Katie Donohoe, Crystal Brunk, Geraldine Hernandez, Tina Jacobucci, Lynda Lazosky, Puneet Mann, Geeta Raval, Ligia Araujo Zampieri, Mypinder 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 Gillrie, Etienne Mahe, Deepa Suryanarayan, Alejandra Ugarte-Torres, Traci Robinson, Mitchell Gibbs, Julia Hewsgirard, Marnie Holmes, Joanna McCarthy, Meagan Ody, Karen Doucette, Wendy Sligl, Ashlesah Sonpar, Kimberley 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 Houston, Yoav Kenyan, Sylvain Lother, Kendiss Olafson, Barret Rush, Terry Wuerz, Dayna Solvason, Lisa Albensi, Soumya Alias, Nora Choi, Laura Curtis, Maureen Hutmacher, Hessam Kashani, Debra Lane, Nicole Marten, Tracey Pronyk-Ward, Lisa Rigaux, Rhonda Silva, Quinn Tays, Renuka Naidu, Jane Mathews, Margaret Mai, Victoria Miceli, Liz Molson, Gayathri Radhakrishnan, Linda Schaefer, Michel 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 Silverman, Eni Nano, Tracey Bentall, Eileen Campbell, Jeffery Kinney, Seema Parvathy, Evridiki Fera, Anthony La Delfa, Jeya Nadarajah, Henry Solow, Edeliza Mendoza, Katrina Engel, Diana Monaco, Laura Kononow, Sutharsan Suntharalingam, Mike Fralick, Laveena Munshi, Samia Saeed, Omar Hajjaj, 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, Nea Okada, Nicholas Pasquale, Romina Ponzielli, Mary Rahmat, Shelina Sabur, Maria Schlag, Leonita Aguiar, Ashmina Damani, Suhyoung Hong, Mona Kokabi, Carolyn Perkins, Juthaporn Cowan, Tony Giulivi, Derek 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 Cheung, Erick Duan, France Clarke, Karlo Matic, Manuel Giraldo, Jennifer Hickey, Ida Lee, Nea Okada, Nicholas Pasquale, Romina Ponzielli, Mary Rahmat, Shelina Sabur, Maria Schlag, Travis Carpenter, Kevin Schwartz, Paril Suthar, Aziz Jiwajee, Daniel Lindsay, Aftab Malik, Brandon Tse, Larissa Matukas, Joel Ray, Shirley Bell, Elizabeth Krok, Ray Guo, Susan John, Vishal Joshi, Jessica Keen, Chris Lazongas, Jacqueline Ostro, Kevin Shore, Jianmin Wang, Jincheol Choi, Pujitha Nallapati, Tina Irwin, Victor Wang, Petra Sheldrake, Neill 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, Samia Saeed, Omar Hajjaj, Maria Kulikova, Sophia 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, Luc 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 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 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 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, Élaine Santos, Julie Trinh Lu, Julien Auger, Marie-Claude Lessard, Louay Mardini, Yves Pesant, Laurie Delves, Lisa Delves, Sophie Denault, Sofia Grigorova, 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 Richard, Marc Fortin, Philippe Gervais, Marie-Ève Boulay, Claudine Ferland, Jakie Guertin, Johane Lepage, Annie Roy, Sarit Assouline, Stephen Caplan, Ling Kong, Christina Canticas, Carley Mayhew, Johanne Ouedraogo, Tévy-Suzy Tep, Gerald Batist, Matthew Cheng, Marina Klein, Nadine Kronfli, Patricia Pelletier, Salman Qureshi, Donald 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, Eve St-Hilaire, Patrick Thibeault, Karine Morin, Gilberte Caissie, Jackie Caissie Collette, Line Daigle, Mélissa Daigle, Bianca Gendron, Nathalie Godin, Angela Lapointe, Gabrielle Moreau, Lola Ouellette-Bernier, Joanne Rockburn, Brigitte Sonier-Ferguson, Christine Wilson, Robert DeSimone, Grant Ellsworth, Rebecca Fry, Noah Goss, Roy 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, Young Kim, Eshan Patel, Sonal Paul, Tiffany Romero, Naima ElBadri, Lina Flores, Tricia Sandoval, Shashi Kapadia, Ljiljana Vasovic, Shanna-Kay Griffiths, Daniel Alvarado, Fiona Goudy, Melissa Lewis, Marina Loizou, Rita Louie, Chantale Pambrun, Sylvia Torrance, Steven Drews, Janet McManus, Oriela Cuevas, Wanda Lafresne, Patrizia Ruoso, Christine Shin, Tony Steed, Rachel Ward, Isabelle Allard, Marc Germain, Sébastien Girard, Éric Parent, Claudia-Mireille Pigeon, Maria Esther Lopes, Margarida Pêcego, Natalia Rosario, Carlos Alexandre da Costa Silva, Thais Oliveira, Maria Cristina Lopes, Sheila Mateos, Lucette Hall, Sarai Paradiso, Donna Strauss, Donald M. Arnold
Journal: Nature Medicine (2021)

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.