Lung aerosol dynamics of airborne influenza A virus-laden droplets and the resultant immune system responses: An in silico study

Influenza A Virus (IAV) replications start from the deposition of inhaled virus-laden droplets on the epithelial cells in the pulmonary tracts. In order to understand the local deposition patterns and within-host dynamics of infectious aerosols, accurate information of high-resolution imaging capabilities, as well as real-time flow cytometry analysis, are required for tracking infected cells, virus agents, and immune system responses. However, clinical and animal studies are in deficit to meet the above-mentioned demands, due to their limited operational flexibility and imaging resolution. Therefore, this study developed an experimentally validated multiscale numerical model, i.e., the Computational Fluid-Particle Dynamics (CFPD) plus Host Cell Dynamics (HCD) model, to predict the transport and deposition of the low-strain IAV-laden droplets, as well as the resultant regional immune system responses. The hygroscopic growth and shrinkage of IAV-laden droplets were also accurately modeled. The subject-specific respiratory system was discretized using polyhedron-core meshes. By recreating both mouth and nasal breathing scenarios, simulations of isotonic IAV-laden droplets with three different compositions were achieved. It is the first time that parametric analysis has been performed to investigate how different exposure conditions can influence the IAV aerodynamics in the lung and the subsequent immune system responses. Numerical results show a higher viral accretion followed by a faster immune system response in the supraglottic region when IAV-laden droplets with the higher NaCl concentration were inhaled. Consequently, more severe symptoms and longer recovery are expected at the pharynx. Furthermore, local deposition patterns of IAV-laden droplets and post-deposition infection dynamics provide direct quantitative evidence to enhance the fundamental understanding of the underlying mechanisms for upper airway and lower airway infections.