[en] Despite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA’s predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies.
Disciplines :
Immunology & infectious disease
Author, co-author :
Brunet-Ratnasingham, Elsa ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Anand, Sai Priya; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada
Gantner, Pierre; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Dyachenko, Alina ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Moquin-Beaudry, Gaël ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Neuroscience, Université de Montréal, Montréal, QC, Canada
Brassard, Nathalie; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Beaudoin-Bussières, Guillaume; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Pagliuzza, Amélie ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Gasser, Romain ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Benlarbi, Mehdi ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Point, Floriane ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Prévost, Jérémie; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Laumaea, Annemarie; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Niessl, Julia ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Nayrac, Manon; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Sannier, Gérémy ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Orban, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada ; Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada
Messier-Peet, Marc; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada
Butler-Laporte, Guillaume ; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
Morrison, David R ; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada
Zhou, Sirui ; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
Nakanishi, Tomoko ; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada ; Department of Human Genetics, McGill University, Montreal, QC, Canada ; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan ; Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, 102-0083 Tokyo, Japan
Boutin, Marianne; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Descôteaux-Dinelle, Jade; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Gendron-Lepage, Gabrielle ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Goyette, Guillaume ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Bourassa, Catherine ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Medjahed, Halima; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Laurent, Laetitia; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada
Rébillard, Rose-Marie ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Neuroscience, Université de Montréal, Montréal, QC, Canada
Richard, Jonathan; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Dubé, Mathieu; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Fromentin, Rémi ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Arbour, Nathalie ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Neuroscience, Université de Montréal, Montréal, QC, Canada
Prat, Alexandre ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Neuroscience, Université de Montréal, Montréal, QC, Canada
Larochelle, Catherine ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Neuroscience, Université de Montréal, Montréal, QC, Canada
Durand, Madeleine ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada
Richards, J Brent; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada ; Department of Human Genetics, McGill University, Montreal, QC, Canada ; Department of Twin Research, King's College London, London, UK
Chassé, Michaël ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada
Tétreault, Martine; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Department of Neuroscience, Université de Montréal, Montréal, QC, Canada
Chomont, Nicolas ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada
Finzi, Andrés ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada ; Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada
Kaufmann, Daniel E ; Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada ; Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada ; Département de Médecine, Université de Montréal, Montréal, QC, Canada
Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality.
Publication date :
26 November 2021
Journal title :
Science Advances
eISSN :
2375-2548
Publisher :
American Association for the Advancement of Science, United States
Volume :
7
Issue :
48
Pages :
eabj5629
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
This work was supported by American Foundation for AIDS Research (amfAR) grant 110068-68-RGCV (to D.E.K., N.C., and A.F.); Canada's COVID-19 Immunity Task Force (CITF), in collaboration with the Canadian Institutes of Health Research (CIHR) grant VR2-173203 (to D.E.K. and A.F.); CIHR grants 365825 and 409511 (to J.B.R.); Canada Foundation for Innovation (CFI): Exceptional Fund COVID-19 grant no. 41027 to A.F., D.E.K., and N.C.; CFI leader to J.B.R.; Ministère de l'Économie et de l'Innovation du Québec, Programme de soutien aux organismes de recherche et d'innovation (to A.F.); CRCHUM Foundation; Fonds de recherche Québec-Santé (FRQS) (BQC-19); Génome Québec (BQC-19); Public Health Agency of Canada (BQC-19); FRQS Merit Research Scholar Award (to D.E.K.); FRQS Salary Award (to N.C., M.Dur., M.C., J.B.R., C.L., and M.T.); FRQS Clinical Research Scholarship (to J.B.R.); Canada Research Chair (to A.F. and A.Pr.); COVID-19 excellence scholarship from the Université de Montréal (to E.B.-R.); CIHR fellowships (to S.P.A. and P.G.); Lady Davis Institute of the JGH (to J.B.R.); NIH Foundation (to J.B.R.); and Cancer Research UK (to J.B.R.).
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