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Visual prediction and parameter optimization of viral dynamics in the mucus milieu of the upper airway based on CFPD-HCD analysis

BACKGROUND AND OBJECTIVE: Respiratory diseases caused by viruses are a major human health problem. To better control the infection and understand the pathogenesis of these diseases, this paper studied SARS-CoV-2, a novel coronavirus outbreak, as an example. METHODS: Based on coupled computational fl...

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Detalles Bibliográficos
Autores principales: Li, Hanyu, Kuga, Kazuki, Ito, Kazuhide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10211256/
https://www.ncbi.nlm.nih.gov/pubmed/37257372
http://dx.doi.org/10.1016/j.cmpb.2023.107622
Descripción
Sumario:BACKGROUND AND OBJECTIVE: Respiratory diseases caused by viruses are a major human health problem. To better control the infection and understand the pathogenesis of these diseases, this paper studied SARS-CoV-2, a novel coronavirus outbreak, as an example. METHODS: Based on coupled computational fluid and particle dynamics (CFPD) and host-cell dynamics (HCD) analyses, we studied the viral dynamics in the mucus layer of the human nasal cavity-nasopharynx. To reproduce the effect of mucociliary movement on the diffusive and convective transport of viruses in the mucus layer, a 3D-shell model was constructed using CT data of the upper respiratory tract (URT) of volunteers. Considering the mucus environment, the HCD model was established by coupling the target cell-limited model with the convection-diffusion term. Parameter optimization of the HCD model is the key problem in the simulation. Therefore, this study focused on the parameter optimization of the viral dynamics model, divided the geometric model into multiple compartments, and used Monolix to perform the nonlinear mixed effects (NLME) of pharmacometrics to discuss the influence of factors such as the number of mucus layers, number of compartments, diffusion rate, and mucus flow velocity on the prediction results. RESULTS: The findings showed that sufficient experimental data can be used to estimate the corresponding parameters of the HCD model. The optimized convection-diffusion case with a two-layer multi-compartment low-velocity model could accurately predict the viral dynamics. CONCLUSIONS: Its visualization process could explain the symptoms of the disease in the nose and contribute to the prevention and targeted treatment of respiratory diseases.