Morgan Craig Slides

Morgan Craig Video

Greg Forest Slides

Greg Forest Video

Morgan Craig Abstract: Delineating the pathophysiological processes that contribute to the development of severe COVID-19 is imperative for improving our understanding of the disease, and for developing improved treatment modalities. Because the identification of causal mechanisms can be experimentally and clinically difficult, we developed a mechanistic, within-host mathematical model and virtual patient cohort to understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19. Our findings identify biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.

Greg Forest Abstract: We build a model that incorporates the detailed physiology of the upper and lower human respiratory tract (RT), including the physical dimensions of each generation of the airway branch geometry and the alveolar space, the thicknesses of the airway surface liquids (ASLs) and their advection velocity from ciliary propulsion in the lower RT.  We further incorporate the diffusivity of SARS-CoV-2 virions in ASLs, tracking their passage through the ASL to encounter the epithelial tissue, the percent surface coverage of infectable epithelial cells and their probability of infection per encounter with infectious virions, the cell latency post infection followed by replication rate and duration of infectious virions shed back into the ASL. From this detailed model and available bounds on infectivity parameters, assuming the individual has no immune response to this novel virus, we focus on understanding of two clinical observations for this presentation: 1. how a high-titer nasal tract infection develops rapidly (~ 2 days) from inhaled exposure to SARS-CoV-2; and 2. how a nasal infection can, and cannot, propagate to alveolar pneumonia in less than a week.  These results raise critical questions that remain open, and that are under intense investigation by us and additional collaborators. This work is based on collaborations by the following team, with papers in preparation: Alex Chen, Cal State Dominguez Hills, former postdoc with Forest and Lai, working on antibody-virus-mucus interactions. Tim Wessler, U. Michigan, former PhD student of Forest and Lai, working on antibody-virus-mucus interactions. Kate Daftari, current PhD student of Forest and Freeman. Kameryn Hinton, current PhD student of Freeman and Forest. Ronit Freeman, UNC Department of Applied Physical Sciences. Sam Lai, UNC Eshelman School of Pharmacy. Ric Boucher, Director, UNC Marsico Lung Institute. Ray Pickles, UNC Marsico Lung Institute and the speaker, Greg Forest, UNC Mathematics, Applied Physical Sciences, and Biomedical Engineering.