Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial
Authors: Bégin Philippe , Callum Jeannie , Jamula Erin , Cook Richard , Heddle Nancy M. , Tinmouth Alan , Zeller Michelle P. , Beaudoin-Bussières Guillaume , Amorim Luiz , Bazin Renée , Loftsgard Kent Cadogan , Carl Richard , Chassé Michaël , Cushing Melissa M. , Daneman Nick , Devine Dana V. , Dumaresq Jeannot , Fergusson Dean A. , Gabe Caroline , Glesby Marshall J. , Li Na , Liu Yang , McGeer Allison , Robitaille Nancy , Sachais Bruce S. , Scales Damon C. , Schwartz Lisa , Shehata Nadine , Turgeon Alexis F. , Wood Heidi , Zarychanski Ryan , Finzi Andrés ,   the CONCOR-1 Study Group, Marceau Danièle , Huang Andy , Carr Holly , Lin Yulia , Lall Rosemarie , Graham Christopher , Arsenault Christine , Sales Valerie , Sidhu Davinder , Semret Makeda , Hamm Caroline , Arhanchiague Eneko , Solh Ziad , Srour Nadim , Soliman Karim , Yee Colin , Laroche Vincent , Nahirniak Susan , Greenaway Christina , Pai Menaka , Côté Andréanne , Tsang Jennifer L. Y. , Cserti-Gazdewich Christine , Talbot Danielle , Poulin Sébastien , Guimaraes Rodrigo , Rushton-Marovac Moira , Langlois Alexandra , Ning Shuoyan , Shih Andrew , Boileau Mélissa , Singh Harjot , Ledingham Donna , Ponnampalam Arjuna , Yan Matthew , Prokopchuk-Gauk Oksana , Poirier André , Girouard Gabriel , Pavenski Katerina , Drouin Olivier , Harris David , Durand Madeleine , Rimmer Emily , Ovakim Daniel , Ménard François , Cuccarolo Glenna , Carruthers Julie , Lucier Kayla , Arsenault Valérie , Auclair Marie-Christine , Avram Meda , Brassard Michael , Cerro Sabrina , Martinez Véronica , Morin Julie , Saint-Jacques Marie , Veillette Maxime , Armali Chantal , Kron Amie , Modi Dimpy , Duncan Joanne , Justumus Pauline , John Melanie St , St-Onge Geneviève , Hadzi-Tosev Milena , Dion Pierre-Marc , McGillivary Lawrence , de Moulliac Andre Valleteau , Nyman Sheila A. , Perilli Stephanie , Van Vliet Paulette Jean , Lane Shannon , Pavenski Katerina , Pereira Rebecca , Sirotich Emily , Abelson Julie , Greene Saara , Khandelwal Aditi , Thakar Swarni , Longo Sarah , Anand Sai Priya , Benlarbi Mehdi , Bourassa Catherine , Boutin Marianne , Descôteaux-Dinelle Jade , Gendron-Lepage Gabrielle , Goyette Guillaume , Laumaea Annemarie , Medjahed Halima , Prévost Jérémie , Richard Jonathan , Kaufmann Daniel , Brunet-Ratnasingham Elsa , Chaumont Nicolas , Drebot Michael , Robinson Alyssia , Mendoza Emelissa , Dimitrova Kristina , Manguiat Kathy , Phillipson Clark , Chan Michael , Evans David , Lin James , Boyer Lucie , Cloutier Marc , Drouin Mathieu , Ducas Éric , Dussault Nathalie , Fournier Marie-Josée , Landy Patricia , Nolin Marie-Ève , Perreault Josée , Tremblay Tony , Nazy Ishac , Xie Feng , Liu David , Wong Michelle , Silverio Gus , Walkus Kristin , Barton Mikaela , Haveman Katherine , Mueller Darlene , Scott Ashley , Moher Matthew , Wood Gordon , Roarty Tracey , Auld Fiona , Carney Gayle , Thomson Virginia , Onell Rodrigo , Walley Keith , Donohoe Katie , Brunk Crystal , Hernandez Geraldine , Jacobucci Tina , Lazosky Lynda , Mann Puneet , Raval Geeta , Zampieri Ligia Araujo , Sekhon Mypinder , Wright Alissa , James Nicola , Chang Gaby , Chen Roy , Deol Kanwal , Gantioqui Jorell , Larsen Elyse , Ramdin Namita , Roche Margaret , Rosinski Kristin , Sham Lawrence , Storms Michelle , Gillrie Mark , Mahe Etienne , Suryanarayan Deepa , Ugarte-Torres Alejandra , Robinson Traci , Gibbs Mitchell , Hewsgirard Julia , Holmes Marnie , McCarthy Joanna , Ody Meagan , Doucette Karen , Sligl Wendy , Sonpar Ashlesah , Robertson Kimberley , Narayan Jeffrey , Ravindran Leka , Stewart Breanne , Zapernick Lori , Lee Stephen , Sy Eric , Wong Alexander , Gryzb Karolina , Craddock Sarah , Fuchs Dennaye , Myrah Danielle , Sunny Sana , Harding Sheila Rutledge , Kogilwaimath Siddarth , Hodgson Nancy , Johnson Dawn , Meier Simona , Thomson Kim , Heendeniya Amila , Houston Brett , Kenyan Yoav , Lother Sylvain , Olafson Kendiss , Rush Barret , Wuerz Terry , Solvason Dayna , Albensi Lisa , Alias Soumya , Choi Nora , Curtis Laura , Hutmacher Maureen , Kashani Hessam , Lane Debra , Marten Nicole , Pronyk-Ward Tracey , Rigaux Lisa , Silva Rhonda , Tays Quinn , Naidu Renuka , Mathews Jane , Mai Margaret , Miceli Victoria , Molson Liz , Radhakrishnan Gayathri , Schaefer Linda , Haddad Michel , Landry Shannon , Chernish Robert , Kruisselbrink Rebecca , Liu Theresa , Jeromin Jayna , Siddiqui Atif , Girolametto Carla , Krokoszynski Kristin , Main Cheryl , Fox-Robichaud Alison , Rochwerg Bram , Kruja Erjona , Ellingham Dana , Sampat Disha , Tang Ngan , Leto Daniela , Karunakaran Meera , Ricciuto Daniel , Fusco Kelly , Ghate Taneera , Robinson Holly , Ball Ian , Shalhoub Sarah , Slessarev Marat , Silverman Michael , Nano Eni , Bentall Tracey , Campbell Eileen , Kinney Jeffery , Parvathy Seema , Fera Evridiki , Delfa Anthony La , Nadarajah Jeya , Solow Henry , Mendoza Edeliza , Engel Katrina , Monaco Diana , Kononow Laura , Suntharalingam Sutharsan , Fralick Mike , Munshi Laveena , Saeed Samia , Hajjaj Omar , Hsu Elaine , Ali Karim , Duan Erick , Farjou George , Jenson Lorraine , Salib Mary , Patterson Lisa , Anant Swati , Ding Josephine , Jomy Jane , Das Pavani , Geagea Anna , Ingber Sarah , Owen Elliot , Lostun Alexandra , Albano Tashea , Chatterjee Antara , Giraldo Manuel , Hickey Jennifer , Lee Ida , Okada Nea , Pasquale Nicholas , Ponzielli Romina , Rahmat Mary , Sabur Shelina , Schlag Maria , Aguiar Leonita , Damani Ashmina , Hong Suhyoung , Kokabi Mona , Perkins Carolyn , Cowan Juthaporn , Giulivi Tony , MacFadden Derek , Cyr Joe , Pecarskie Amanda , Porteous Rebecca , Vedder Priscila Ogawa , Watpool Irene , Berardi Phil , Bustani Laith , Graver Alison , Iyengar Akshai , Kisilewicz Magdalena , Majewski Jake , Marovac Misha , Murthy Ruchi , Sharma Karan , Walcer Marina , Chagla Zain , Cheung Jason , Duan Erick , Clarke France , Matic Karlo , Giraldo Manuel , Hickey Jennifer , Lee Ida , Okada Nea , Pasquale Nicholas , Ponzielli Romina , Rahmat Mary , Sabur Shelina , Schlag Maria , Carpenter Travis , Schwartz Kevin , Suthar Paril , Jiwajee Aziz , Lindsay Daniel , Malik Aftab , Tse Brandon , Matukas Larissa , Ray Joel , Bell Shirley , Krok Elizabeth , Guo Ray , John Susan , Joshi Vishal , Keen Jessica , Lazongas Chris , Ostro Jacqueline , Shore Kevin , Wang Jianmin , Choi Jincheol , Nallapati Pujitha , Irwin Tina , Wang Victor , Sheldrake Petra , Adhikari Neill , Wunsch Hannah , Bailey Jacob , Meirovich Harley , Colavecchia Connie , Kahwash Eiad , Sud Sachin , Romano Martin , Coburn Bryan , Del Sorbo Lorenzo , Granton John , Husain Shahid , Pendergrast Jacob , Sharkawy Abdu , Wilcox Liz , Saeed Samia , Hajjaj Omar , Kulikova Maria , Massin Sophia , Kennette Wendy , Mazzetti Ian , Naccarato Krista , Park Grace , Pennetti Alex , Primeau Corrin , Vilag Cathy , Lapointe Yves , Lemay Anne-Sophie , Duceppe Emmanuelle , Rioux-Massé Benjamin , Tremblay Cécile , Arlotto Pascale , Bouchard Claudia , Matte Stephanie , Messier-Peet Marc , Francoeur Charles-Langis , Lauzier François , Leblanc Guillaume , Bellemare David , Cloutier Ève , Costerousse Olivier , Chénard Émilie Couillard , Daher Rana , Daigle Marjorie , Grenier Stéphanie , Guilbeault Gabrielle , Rioux Marie-Pier , St-Onge Maude , Tremblay Antoine , Beaudoin Brian , Lanthier Luc , Larrivée Pierre , Morin Pierre-Aurèle , Carbonneau Élaine , Lacasse Robert , Autmizguine Julie , Boucoiran Isabelle , Du Pont-Thibodeau Geneviève , La Haye Annie , Lague Vincent , Léveillé Karine , Quach-Thanh Caroline , Émériaud Guillaume , Jouvet Philippe , Haddad Élie , Turgeon-Provost Camille , Fox Susan , Baldé Diaraye , Ménard Lorraine , Morissette Suzanne , Schnorr-Meloche Miriam , Turcotte Andrée-Anne , Vallée Caroline , Castonguay Stéphanie , Nguyen Tuyen , Rivest Natalie , Roussos Marios , Simoneau Esther , Belecciu Andreea , Bouchard Marie-Hélène , Daviau Eric , Martin Cynthia , Sabourin Nicole , Tremblay Solange , Gagné Émilie , Gagné Nancy-Lisa , Larouche Julie , Larouche Vanessa , Tremblay Véronick , Tremblay Vicky , Blanchette Pierre , Claveau David , Lamarre Marianne , Tapps Danielle , Albert Martin , Duca Anatolie , Leduc Jean-Michel , Boudreault-Pedneault Jean-Samuel , Barsalou Annie , Deschênes-Dion Suzanne , Ibrahim Stéphanie , Ridyard Stéphanie , Rousseau Julie , Ahern Stéphane , Arsenault Marie-Pier , Dufresne Simon-Frédéric , Mollica Luigina , Wang Hang Ting , Beau Soizic , Beaupré Dominique , Dégarie Marjolaine , Delorme Iris , Farkas Melissa , Gratton Michel-Olivier , Guertin Arnaud , Jalbert Guylaine , Meilleur Mélanie , Labrecque Charles Ratté , Santos Élaine , Lu Julie Trinh , Auger Julien , Lessard Marie-Claude , Mardini Louay , Pesant Yves , Delves Laurie , Delves Lisa , Denault Sophie , Grigorova Sofia , Lambert Michelle , Langille Nathalie , Langlois Corinne , Rock Caroline , Sardin-Laframboise Yannick , Archambault Patrick , Bélanger-Pelletier Joannie , Duquet-Deblois Estel , Dupuis-Picard Vanessa , Hamelin Yannick , Leduc Samuel , Richard Mélanie , Fortin Marc , Gervais Philippe , Boulay Marie-Ève , Ferland Claudine , Guertin Jakie , Lepage Johane , Roy Annie , Assouline Sarit , Caplan Stephen , Kong Ling , Canticas Christina , Mayhew Carley , Ouedraogo Johanne , Tep Tévy-Suzy , Batist Gerald , Cheng Matthew , Klein Marina , Kronfli Nadine , Pelletier Patricia , Qureshi Salman , Vinh Donald , Dziarmaga Robert , Peiris Hansi , Proulx-Boucher Karène , Roger Jonathan , Rothschild Molly-Ann , Yuen Chung-Yan , Barkati Sapha , Routy Jean-Pierre , Sinanan-Pelletier Sondra , LeBlanc Rémi , St-Hilaire Eve , Thibeault Patrick , Morin Karine , Caissie Gilberte , Collette Jackie Caissie , Daigle Line , Daigle Mélissa , Gendron Bianca , Godin Nathalie , Lapointe Angela , Moreau Gabrielle , Ouellette-Bernier Lola , Rockburn Joanne , Sonier-Ferguson Brigitte , Wilson Christine , DeSimone Robert , Ellsworth Grant , Fry Rebecca , Goss Noah , Gulick Roy , Vaamonde Carlos , Wilkin Timothy , Arar Celine , Berardi Jonathan , Chen Dennis , Garcia-Miller Cristina , Goldbach Arthur , Gripp Lauren , Hayden Danielle , Kane Kathleen , Li Jiamin , Marcelin Kinge-Ann , Megill Christina , Nelson Meredith , Paguntalan Ailema , Raab Gabriel , Resso Gianna , Rosario Roxanne , Rossen Noah , Tamura Shoran , Zhao Ethan , Goss Cheryl , Kim Young , Patel Eshan , Paul Sonal , Romero Tiffany , ElBadri Naima , Flores Lina , Sandoval Tricia , Kapadia Shashi , Vasovic Ljiljana , Griffiths Shanna-Kay , Alvarado Daniel , Goudy Fiona , Lewis Melissa , Loizou Marina , Louie Rita , Pambrun Chantale , Torrance Sylvia , Drews Steven , McManus Janet , Cuevas Oriela , Lafresne Wanda , Ruoso Patrizia , Shin Christine , Steed Tony , Ward Rachel , Allard Isabelle , Germain Marc , Girard Sébastien , Parent Éric , Pigeon Claudia-Mireille , Lopes Maria Esther , Pêcego Margarida , Rosario Natalia , da Costa Silva Carlos Alexandre , Oliveira Thais , Lopes Maria Cristina , Mateos Sheila , Hall Lucette , Paradiso Sarai , Strauss Donna , Arnold Donald M. 
Published: September 2021

AbstractThe 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.