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Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort

Nadège Néant 1, * Guillaume Lingas 1 Quentin Le Hingrat 1 Jade Ghosn 2 Ilka Engelmann 3 Quentin Lepiller 4, 5 Alexandre Gaymard 6 Virginie Ferré 7 Cédric Hartard 8 Jean-Christophe Plantier 9 V. Thibault 10 Julien Marlet 11 Brigitte Montes 12 Kevin Bouiller 13, 5 François-Xavier Lescure 2 Jean-François Timsit 1, 14 Emmanuel Faure 15 Julien Poissy 16 Christian Chidiac 17 François Raffi 18 Antoine Kimmoun 19, 20, 21, 22 Manuel Etienne 23 Jean-Christophe Richard 24 Pierre Tattevin 10, 25 Denis Garot 26 Vincent Le Moing 27 Delphine Bachelet 28 Coralie Tardivon 28 Xavier Duval 1, 29 Yazdan Yazdanpanah 1 France Mentré 1 Cédric Laouénan 1 Benoit Visseaux 1 Jérémie Guedj 1
* Corresponding author
Abstract : The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients ( P < 10 −4 ). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10 −3 ). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.
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Submitted on : Monday, October 25, 2021 - 4:54:32 PM
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Nadège Néant, Guillaume Lingas, Quentin Le Hingrat, Jade Ghosn, Ilka Engelmann, et al.. Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2021, 118 (8), pp.e2017962118. ⟨10.1073/pnas.2017962118⟩. ⟨hal-03364267⟩

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