  Investigations on airborne transmission of pathogens constitute a rapidly
expanding field, primarily focused on understanding the expulsion patterns of
respiratory particulates from infected hosts and their dispersion in confined
spaces. Largely overlooked has been the crucial role of fluid dynamics in
guiding inhaled virus-laden particulates within the respiratory cavity, thereby
directing the pathogens to the infection-prone upper airway sites. Here, we
discuss a multi-scale approach for modeling the onset parameters of airway
infection based on flow physics. The findings are backed by Large Eddy
Simulations of inhaled airflow and computed trajectories of pathogen-bearing
aerosols/droplets within two clinically healthy and anatomically realistic
airway geometries reconstructed from computed tomography imaging. As a
representative anisotropic pathogen that can transmit aerially, we have picked
smallpox from the Poxviridae family to demonstrate the approach. The fluid
dynamics findings on inhaled transmission trends are integrated with
virological and epidemiological parameters for smallpox (e.g., viral
concentration in host ejecta, physical properties of virions, and typical
exposure durations) to establish the corresponding infectious dose (i.e., the
number of virions potent enough to launch infection in an exposed subject) to
be, at maximum, of the order of O(2), or more precisely 1 to 180. The
projection agrees remarkably well with the known virological parameters for
smallpox.
