A PDE model for the localization and spread of flu in the human respiratory tract

Within the human respiratory tract (HRT), virus diffuses through the periciliary fluid (PCF) bathing the epithelium. But it also undergoes advection: as the mucus layer sitting atop the PCF is pushed along by the ciliated cell's beating cilia, the PCF and its virus contents are also pushed along, upwards towards the nose and mouth. Our PDE model represents the HRT as a one-dimensional track extending from the nose down to the lower HRT, wherein stationary cells interact with virus which moves within (diffusion) and along with (advection) the PCF. In the PDE model, diffusion is negligible in the presence of advection which effectively sweeps away virus, preventing infection from spreading below the depth of deposition. Higher virus production rates (10-fold) are required at higher advection speeds (40 micron/s) to maintain equivalent infection severity and timing. Because virus is entrained upwards, upper parts of the HRT located downstream of the advection flow see more virus than lower parts, and so infection grows, peaks, and resolves later in the lower HRT. Clinically, the infection would appear to progress from the upper towards the lower HRT, as reported in mice. When the PDE model is expanded to include cellular regeneration and an immune response, it reproduces tissue damage levels reported in patients. This new PDE model offers a convenient and unique platform from which to study the localization and spread of respiratory viruses (flu, RSV, COVID-19) within the HRT during an infection.