Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality
Elsa Brunet‐Ratnasingham, Sai Priya Anand, Pierre Gantner, Alina Dyachenko, Gaël Moquin‐Beaudry, Nathalie Brassard, Guillaume Beaudoin-Bussières, Amélie Pagliuzza, Romain Gasser, Mehdi Benlarbi, Floriane Point, Jérémie Prévost, Annemarie Laumaea, Julia Niessl, Manon Nayrac, Gérémy Sannier, Catherine Orban, Marc Messier-Peet, Guillaume Butler‐Laporte, David Morrison, Sirui Zhou, Tomoko Nakanishi, Marianne Boutin, Jade Descôteaux-Dinelle, Gabrielle Gendron‐Lepage, Guillaume Goyette, Catherine Bourassa, Halima Medjahed, Lætitia Laurent, Rose‐Marie Rébillard, Jonathan Richard, Mathieu Dubé, Rémi Fromentin, Nathalie Arbour, Alexandre Prat, Catherine Larochelle, Madéleine Durand, J. Brent Richards, Michaël Chassé, Martine Tétreault, Nicolas Chomont, Andrés Finzi, Daniel E. Kaufmann
Abstract
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.