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 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.

Prediction of transport, deposition, and resultant immune response of nasal spray vaccine droplets using a CFPD-HCD model in a 6-year-old upper airway geometry to potentially prevent COVID-19.

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the angiotensin-converting-enzyme-2-rich region, i.e., the olfactory region (OR), in the nasal cavity of a 6-year-old female to possibly prevent corona virus disease 19 (COVID-19). To investigate how administration strategy can influence nasal vaccine efficiency, a validated multi-scale model, i.e., computational fluid-particle dynamics (CFPD) and host-cell dynamics (HCD) model, was employed. Droplet deposition fraction, size change, residence time, and the area percentage of OR covered by the vaccine droplets, and triggered immune system response were predicted with different spray cone angles, initial droplet velocities, and compositions. Numerical results indicate that droplet initial velocity and composition have negligible influences on the vaccine delivery efficiency to OR. In contrast, the spray cone angle can significantly impact the vaccine delivery efficiency. The triggered immunity was not significantly influenced by the administration investigated in this study due to the low percentage of OR area covered by the droplets. To enhance the effectiveness of the intranasal vaccine to prevent COVID-19 infection, it is necessary to optimize the vaccine formulation and administration strategy so that the vaccine droplets can cover more epithelial cells in OR to minimize the number of available receptors for SARS-CoV-2.

SARS-CoV-2 Dynamics in the Mucus Layer of the Human Upper Respiratory Tract Based on Host–Cell Dynamics

A thorough understanding of the inhalation dynamics of infectious aerosols indoors and infection dynamics within the host by inhaled viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in the assessment and control of infection risks indoors. Here, by combining computational fluid–particle dynamics (CFPD) and host–cell dynamics (HCD), SARS-CoV-2 infection dynamics in the mucus layer of the human upper airway were studied. To reproduce the diffusive and convective transport of the virus in the nasal cavity–nasopharynx by mucociliary motion, a three-dimensional (3D)-shell model with a mucus layer was developed. The initial virus concentrations for HCD calculation were estimated based on the deposition distribution of droplets with representative sizes analyzed by CFPD. To develop a new HCD model, the target-cell-limited model was integrated with the convection–diffusion equation. Additionally, the sensitivity of the infection rate β to the infection dynamics was systematically investigated. The results showed that the time series of SARS-CoV-2 concentration in the mucus layer strongly depended on diffusion, convection, and β. Although the SARS-CoV-2 dynamics obtained here have not been verified by corresponding clinical data, they can preliminarily reveal its transmission mode in the upper airway, which will contribute to the prevention and treatment of coronavirus disease 2019.