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Article Dans Une Revue CPT: Pharmacometrics & Systems Pharmacology Année : 2023

Association between SARS‐CoV‐2 viral kinetics and clinical score evolution in hospitalized patients

Richard Greil
  • Fonction : Auteur

Résumé

The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS‐2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020‐000936‐23) randomly assigned to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS‐2 score lower than 3 (in patients with NEWS‐2 <7 at hospitalization) or 5 (in patients with NEWS‐2 ≥7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS‐2. However, simulations predicted that antiviral activity greater than 99% could reduce by 2 days the time to clinical improvement in patients with high viral load, irrespective of the NEWS‐2 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.
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Dates et versions

hal-04489634 , version 1 (05-03-2024)

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Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Nadège Néant, Guillaume Lingas, Alexandre Gaymard, Drifa Belhadi, Maya Hites, et al.. Association between SARS‐CoV‐2 viral kinetics and clinical score evolution in hospitalized patients. CPT: Pharmacometrics & Systems Pharmacology, 2023, CPT: Pharmacometrics & Systems Pharmacology, 1212, pp.2027-2037. ⟨10.1002/psp4.13051⟩. ⟨hal-04489634⟩
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