Association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients.
Journal
CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011
Informations de publication
Date de publication:
20 Sep 2023
20 Sep 2023
Historique:
revised:
27
08
2023
received:
15
02
2023
accepted:
05
09
2023
pubmed:
20
9
2023
medline:
20
9
2023
entrez:
20
9
2023
Statut:
aheadofprint
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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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