Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.
Adult
Aged
Aged, 80 and over
Brazil
/ epidemiology
COVID-19
/ epidemiology
Canada
/ epidemiology
Female
Hospitalization
/ statistics & numerical data
Humans
Immunization, Passive
Intention to Treat Analysis
Male
Middle Aged
SARS-CoV-2
/ immunology
Treatment Outcome
United States
/ epidemiology
COVID-19 Serotherapy
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
18
06
2021
accepted:
02
08
2021
pubmed:
11
9
2021
medline:
15
12
2021
entrez:
10
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34504336
doi: 10.1038/s41591-021-01488-2
pii: 10.1038/s41591-021-01488-2
pmc: PMC8604729
doi:
Banques de données
ClinicalTrials.gov
['NCT04348656']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2012-2024Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec)
ID : 281662
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : 447352
Investigateurs
Danièle Marceau
(D)
Andy Huang
(A)
Holly Carr
(H)
Yulia Lin
(Y)
Rosemarie Lall
(R)
Christopher Graham
(C)
Christine Arsenault
(C)
Valerie Sales
(V)
Davinder Sidhu
(D)
Makeda Semret
(M)
Caroline Hamm
(C)
Eneko Arhanchiague
(E)
Ziad Solh
(Z)
Nadim Srour
(N)
Karim Soliman
(K)
Colin Yee
(C)
Vincent Laroche
(V)
Susan Nahirniak
(S)
Christina Greenaway
(C)
Menaka Pai
(M)
Andréanne Côté
(A)
Jennifer L Y Tsang
(JLY)
Christine Cserti-Gazdewich
(C)
Danielle Talbot
(D)
Sébastien Poulin
(S)
Rodrigo Guimaraes
(R)
Moira Rushton-Marovac
(M)
Alexandra Langlois
(A)
Shuoyan Ning
(S)
Andrew Shih
(A)
Mélissa Boileau
(M)
Harjot Singh
(H)
Donna Ledingham
(D)
Arjuna Ponnampalam
(A)
Matthew Yan
(M)
Oksana Prokopchuk-Gauk
(O)
André Poirier
(A)
Gabriel Girouard
(G)
Katerina Pavenski
(K)
Olivier Drouin
(O)
David Harris
(D)
Madeleine Durand
(M)
Emily Rimmer
(E)
Daniel Ovakim
(D)
François Ménard
(F)
Glenna Cuccarolo
(G)
Julie Carruthers
(J)
Kayla Lucier
(K)
Valérie Arsenault
(V)
Marie-Christine Auclair
(MC)
Meda Avram
(M)
Michael Brassard
(M)
Sabrina Cerro
(S)
Véronica Martinez
(V)
Julie Morin
(J)
Marie Saint-Jacques
(M)
Maxime Veillette
(M)
Chantal Armali
(C)
Amie Kron
(A)
Dimpy Modi
(D)
Joanne Duncan
(J)
Pauline Justumus
(P)
Melanie St John
(MS)
Geneviève St-Onge
(G)
Milena Hadzi-Tosev
(M)
Pierre-Marc Dion
(PM)
Lawrence McGillivary
(L)
Andre Valleteau de Moulliac
(AV)
Sheila A Nyman
(SA)
Stephanie Perilli
(S)
Paulette Jean Van Vliet
(PJ)
Shannon Lane
(S)
Katerina Pavenski
(K)
Rebecca Pereira
(R)
Emily Sirotich
(E)
Julie Abelson
(J)
Saara Greene
(S)
Aditi Khandelwal
(A)
Swarni Thakar
(S)
Sarah Longo
(S)
Sai Priya Anand
(SP)
Mehdi Benlarbi
(M)
Catherine Bourassa
(C)
Marianne Boutin
(M)
Jade Descôteaux-Dinelle
(J)
Gabrielle Gendron-Lepage
(G)
Guillaume Goyette
(G)
Annemarie Laumaea
(A)
Halima Medjahed
(H)
Jérémie Prévost
(J)
Jonathan Richard
(J)
Daniel Kaufmann
(D)
Elsa Brunet-Ratnasingham
(E)
Nicolas Chaumont
(N)
Michael Drebot
(M)
Alyssia Robinson
(A)
Emelissa Mendoza
(E)
Kristina Dimitrova
(K)
Kathy Manguiat
(K)
Clark Phillipson
(C)
Michael Chan
(M)
David Evans
(D)
James Lin
(J)
Lucie Boyer
(L)
Marc Cloutier
(M)
Mathieu Drouin
(M)
Éric Ducas
(É)
Nathalie Dussault
(N)
Marie-Josée Fournier
(MJ)
Patricia Landy
(P)
Marie-Ève Nolin
(MÈ)
Josée Perreault
(J)
Tony Tremblay
(T)
Ishac Nazy
(I)
Feng Xie
(F)
David Liu
(D)
Michelle Wong
(M)
Gus Silverio
(G)
Kristin Walkus
(K)
Mikaela Barton
(M)
Katherine Haveman
(K)
Darlene Mueller
(D)
Ashley Scott
(A)
Matthew Moher
(M)
Gordon Wood
(G)
Tracey Roarty
(T)
Fiona Auld
(F)
Gayle Carney
(G)
Virginia Thomson
(V)
Rodrigo Onell
(R)
Keith Walley
(K)
Katie Donohoe
(K)
Crystal Brunk
(C)
Geraldine Hernandez
(G)
Tina Jacobucci
(T)
Lynda Lazosky
(L)
Puneet Mann
(P)
Geeta Raval
(G)
Ligia Araujo Zampieri
(LA)
Mypinder Sekhon
(M)
Alissa Wright
(A)
Nicola James
(N)
Gaby Chang
(G)
Roy Chen
(R)
Kanwal Deol
(K)
Jorell Gantioqui
(J)
Elyse Larsen
(E)
Namita Ramdin
(N)
Margaret Roche
(M)
Kristin Rosinski
(K)
Lawrence Sham
(L)
Michelle Storms
(M)
Mark Gillrie
(M)
Etienne Mahe
(E)
Deepa Suryanarayan
(D)
Alejandra Ugarte-Torres
(A)
Traci Robinson
(T)
Mitchell Gibbs
(M)
Julia Hewsgirard
(J)
Marnie Holmes
(M)
Joanna McCarthy
(J)
Meagan Ody
(M)
Karen Doucette
(K)
Wendy Sligl
(W)
Ashlesah Sonpar
(A)
Kimberley Robertson
(K)
Jeffrey Narayan
(J)
Leka Ravindran
(L)
Breanne Stewart
(B)
Lori Zapernick
(L)
Stephen Lee
(S)
Eric Sy
(E)
Alexander Wong
(A)
Karolina Gryzb
(K)
Sarah Craddock
(S)
Dennaye Fuchs
(D)
Danielle Myrah
(D)
Sana Sunny
(S)
Sheila Rutledge Harding
(SR)
Siddarth Kogilwaimath
(S)
Nancy Hodgson
(N)
Dawn Johnson
(D)
Simona Meier
(S)
Kim Thomson
(K)
Amila Heendeniya
(A)
Brett Houston
(B)
Yoav Kenyan
(Y)
Sylvain Lother
(S)
Kendiss Olafson
(K)
Barret Rush
(B)
Terry Wuerz
(T)
Dayna Solvason
(D)
Lisa Albensi
(L)
Soumya Alias
(S)
Nora Choi
(N)
Laura Curtis
(L)
Maureen Hutmacher
(M)
Hessam Kashani
(H)
Debra Lane
(D)
Nicole Marten
(N)
Tracey Pronyk-Ward
(T)
Lisa Rigaux
(L)
Rhonda Silva
(R)
Quinn Tays
(Q)
Renuka Naidu
(R)
Jane Mathews
(J)
Margaret Mai
(M)
Victoria Miceli
(V)
Liz Molson
(L)
Gayathri Radhakrishnan
(G)
Linda Schaefer
(L)
Michel Haddad
(M)
Shannon Landry
(S)
Robert Chernish
(R)
Rebecca Kruisselbrink
(R)
Theresa Liu
(T)
Jayna Jeromin
(J)
Atif Siddiqui
(A)
Carla Girolametto
(C)
Kristin Krokoszynski
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Cheryl Main
(C)
Alison Fox-Robichaud
(A)
Bram Rochwerg
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Erjona Kruja
(E)
Dana Ellingham
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Disha Sampat
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Ngan Tang
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Daniela Leto
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Meera Karunakaran
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Daniel Ricciuto
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Kelly Fusco
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Taneera Ghate
(T)
Holly Robinson
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Ian Ball
(I)
Sarah Shalhoub
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Marat Slessarev
(M)
Michael Silverman
(M)
Eni Nano
(E)
Tracey Bentall
(T)
Eileen Campbell
(E)
Jeffery Kinney
(J)
Seema Parvathy
(S)
Evridiki Fera
(E)
Anthony La Delfa
(A)
Jeya Nadarajah
(J)
Henry Solow
(H)
Edeliza Mendoza
(E)
Katrina Engel
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Diana Monaco
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(L)
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(S)
Omar Hajjaj
(O)
Elaine Hsu
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(J)
Jincheol Choi
(J)
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(T)
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(V)
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(J)
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(C)
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Martin Romano
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(B)
Lorenzo Del Sorbo
(L)
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(J)
Shahid Husain
(S)
Jacob Pendergrast
(J)
Abdu Sharkawy
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Liz Wilcox
(L)
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(S)
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(O)
Maria Kulikova
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(S)
Wendy Kennette
(W)
Ian Mazzetti
(I)
Krista Naccarato
(K)
Grace Park
(G)
Alex Pennetti
(A)
Corrin Primeau
(C)
Cathy Vilag
(C)
Yves Lapointe
(Y)
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(AS)
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(E)
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(B)
Cécile Tremblay
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Pascale Arlotto
(P)
Claudia Bouchard
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Stephanie Matte
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Marc Messier-Peet
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Charles-Langis Francoeur
(CL)
François Lauzier
(F)
Guillaume Leblanc
(G)
David Bellemare
(D)
Ève Cloutier
(È)
Olivier Costerousse
(O)
Émilie Couillard Chénard
(ÉC)
Rana Daher
(R)
Marjorie Daigle
(M)
Stéphanie Grenier
(S)
Gabrielle Guilbeault
(G)
Marie-Pier Rioux
(MP)
Maude St-Onge
(M)
Antoine Tremblay
(A)
Brian Beaudoin
(B)
Luc Lanthier
(L)
Pierre Larrivée
(P)
Pierre-Aurèle Morin
(PA)
Élaine Carbonneau
(É)
Robert Lacasse
(R)
Julie Autmizguine
(J)
Isabelle Boucoiran
(I)
Geneviève Du Pont-Thibodeau
(G)
Annie La Haye
(A)
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(V)
Karine Léveillé
(K)
Caroline Quach-Thanh
(C)
Guillaume Émériaud
(G)
Philippe Jouvet
(P)
Élie Haddad
(É)
Camille Turgeon-Provost
(C)
Susan Fox
(S)
Diaraye Baldé
(D)
Lorraine Ménard
(L)
Suzanne Morissette
(S)
Miriam Schnorr-Meloche
(M)
Andrée-Anne Turcotte
(AA)
Caroline Vallée
(C)
Stéphanie Castonguay
(S)
Tuyen Nguyen
(T)
Natalie Rivest
(N)
Marios Roussos
(M)
Esther Simoneau
(E)
Andreea Belecciu
(A)
Marie-Hélène Bouchard
(MH)
Eric Daviau
(E)
Cynthia Martin
(C)
Nicole Sabourin
(N)
Solange Tremblay
(S)
Émilie Gagné
(É)
Nancy-Lisa Gagné
(NL)
Julie Larouche
(J)
Vanessa Larouche
(V)
Véronick Tremblay
(V)
Vicky Tremblay
(V)
Pierre Blanchette
(P)
David Claveau
(D)
Marianne Lamarre
(M)
Danielle Tapps
(D)
Martin Albert
(M)
Anatolie Duca
(A)
Jean-Michel Leduc
(JM)
Jean-Samuel Boudreault-Pedneault
(JS)
Annie Barsalou
(A)
Suzanne Deschênes-Dion
(S)
Stéphanie Ibrahim
(S)
Stéphanie Ridyard
(S)
Julie Rousseau
(J)
Stéphane Ahern
(S)
Marie-Pier Arsenault
(MP)
Simon-Frédéric Dufresne
(SF)
Luigina Mollica
(L)
Hang Ting Wang
(HT)
Soizic Beau
(S)
Dominique Beaupré
(D)
Marjolaine Dégarie
(M)
Iris Delorme
(I)
Melissa Farkas
(M)
Michel-Olivier Gratton
(MO)
Arnaud Guertin
(A)
Guylaine Jalbert
(G)
Mélanie Meilleur
(M)
Charles Ratté Labrecque
(CR)
Élaine Santos
(É)
Julie Trinh Lu
(JT)
Julien Auger
(J)
Marie-Claude Lessard
(MC)
Louay Mardini
(L)
Yves Pesant
(Y)
Laurie Delves
(L)
Lisa Delves
(L)
Sophie Denault
(S)
Sofia Grigorova
(S)
Michelle Lambert
(M)
Nathalie Langille
(N)
Corinne Langlois
(C)
Caroline Rock
(C)
Yannick Sardin-Laframboise
(Y)
Patrick Archambault
(P)
Joannie Bélanger-Pelletier
(J)
Estel Duquet-Deblois
(E)
Vanessa Dupuis-Picard
(V)
Yannick Hamelin
(Y)
Samuel Leduc
(S)
Mélanie Richard
(M)
Marc Fortin
(M)
Philippe Gervais
(P)
Marie-Ève Boulay
(MÈ)
Claudine Ferland
(C)
Jakie Guertin
(J)
Johane Lepage
(J)
Annie Roy
(A)
Sarit Assouline
(S)
Stephen Caplan
(S)
Ling Kong
(L)
Christina Canticas
(C)
Carley Mayhew
(C)
Johanne Ouedraogo
(J)
Tévy-Suzy Tep
(TS)
Gerald Batist
(G)
Matthew Cheng
(M)
Marina Klein
(M)
Nadine Kronfli
(N)
Patricia Pelletier
(P)
Salman Qureshi
(S)
Donald Vinh
(D)
Robert Dziarmaga
(R)
Hansi Peiris
(H)
Karène Proulx-Boucher
(K)
Jonathan Roger
(J)
Molly-Ann Rothschild
(MA)
Chung-Yan Yuen
(CY)
Sapha Barkati
(S)
Jean-Pierre Routy
(JP)
Sondra Sinanan-Pelletier
(S)
Rémi LeBlanc
(R)
Eve St-Hilaire
(E)
Patrick Thibeault
(P)
Karine Morin
(K)
Gilberte Caissie
(G)
Jackie Caissie Collette
(JC)
Line Daigle
(L)
Mélissa Daigle
(M)
Bianca Gendron
(B)
Nathalie Godin
(N)
Angela Lapointe
(A)
Gabrielle Moreau
(G)
Lola Ouellette-Bernier
(L)
Joanne Rockburn
(J)
Brigitte Sonier-Ferguson
(B)
Christine Wilson
(C)
Robert DeSimone
(R)
Grant Ellsworth
(G)
Rebecca Fry
(R)
Noah Goss
(N)
Roy Gulick
(R)
Carlos Vaamonde
(C)
Timothy Wilkin
(T)
Celine Arar
(C)
Jonathan Berardi
(J)
Dennis Chen
(D)
Cristina Garcia-Miller
(C)
Arthur Goldbach
(A)
Lauren Gripp
(L)
Danielle Hayden
(D)
Kathleen Kane
(K)
Jiamin Li
(J)
Kinge-Ann Marcelin
(KA)
Christina Megill
(C)
Meredith Nelson
(M)
Ailema Paguntalan
(A)
Gabriel Raab
(G)
Gianna Resso
(G)
Roxanne Rosario
(R)
Noah Rossen
(N)
Shoran Tamura
(S)
Ethan Zhao
(E)
Cheryl Goss
(C)
Young Kim
(Y)
Eshan Patel
(E)
Sonal Paul
(S)
Tiffany Romero
(T)
Naima ElBadri
(N)
Lina Flores
(L)
Tricia Sandoval
(T)
Shashi Kapadia
(S)
Ljiljana Vasovic
(L)
Shanna-Kay Griffiths
(SK)
Daniel Alvarado
(D)
Fiona Goudy
(F)
Melissa Lewis
(M)
Marina Loizou
(M)
Rita Louie
(R)
Chantale Pambrun
(C)
Sylvia Torrance
(S)
Steven Drews
(S)
Janet McManus
(J)
Oriela Cuevas
(O)
Wanda Lafresne
(W)
Patrizia Ruoso
(P)
Christine Shin
(C)
Tony Steed
(T)
Rachel Ward
(R)
Isabelle Allard
(I)
Marc Germain
(M)
Sébastien Girard
(S)
Éric Parent
(É)
Claudia-Mireille Pigeon
(CM)
Maria Esther Lopes
(ME)
Margarida Pêcego
(M)
Natalia Rosario
(N)
Carlos Alexandre da Costa Silva
(CA)
Thais Oliveira
(T)
Maria Cristina Lopes
(MC)
Sheila Mateos
(S)
Lucette Hall
(L)
Sarai Paradiso
(S)
Donna Strauss
(D)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
Références
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