Structure and Hierarchy of SARS-CoV-2 Infection Dynamics Models Revealed by Reaction Network Analysis.

This work provides a mathematical technique for analyzing and comparing infection dynamics models with respect to their potential long-term behavior, resulting in a hierarchy integrating all models. We apply our technique to coupled ordinary and partial differential equation models of SARS-CoV-2 infection dynamics operating on different scales, that is, within a single organism and between several hosts. The structure of a model is assessed by the theory of chemical organizations, not requiring quantitative kinetic information. We present the Hasse diagrams of organizations for the twelve virus models analyzed within this study. For comparing models, each organization is characterized by the types of species it contains. For this, each species is mapped to one out of four types, representing uninfected, infected, immune system, and bacterial species, respectively. Subsequently, we can integrate these results with those of our former work on Influenza-A virus resulting in a single joint hierarchy of 24 models. It appears that the SARS-CoV-2 models are simpler with respect to their long term behavior and thus display a simpler hierarchy with little dependencies compared to the Influenza-A models. Our results can support further development towards more complex SARS-CoV-2 models targeting the higher levels of the hierarchy.