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  1. SARS-CoV-2 continues to upend human life by posing novel threats related to disease spread and mutations. Current models for the disease burden of SARS-CoV-2 consider the aggregate nature of the virus without differentiating between the potency of its multiple strains. Hence, there is a need to create a fundamental modeling framework for multi-strain viruses that considers the competing viral pathogenic pathways. Alongside the consideration that other viral pathogens may coexist, there is also a need for a generalizable modeling framework to account for multiple epidemics (i.e., multi-demics) scenarios, such as influenza and COVID-19 occurring simultaneously. We present a fundamental network thermodynamics approach for assessing, determining, and predicting viral outbreak severity, which extends well-known standard epidemiological models. In particular, we use historical data from New York City’s 2011–2019 influenza seasons and SARS-CoV-2 spread to identify the model parameters. In our model-based analysis, we employ a standard susceptible–infected–recovered (SIR) model with pertinent generalizations to account for multi-strain and multi-demics scenarios. We show that the reaction affinities underpinning the formation processes of our model can be used to categorize the severity of infectious or deceased populations. The spontaneity of occurrence captured by the change in Gibbs free energy of reaction (ΔG) in themore »system suggests the stability of forward occurring population transfers. The magnitude of ΔG is used to examine past influenza outbreaks and infer epidemiological factors, such as mortality and case burden. This method can be extrapolated for wide-ranging utility in computational epidemiology. The risk of overlapping multi-demics seasons between influenza and SARS-CoV-2 will persist as a significant threat in forthcoming years. Further, the possibility of mutating strains requires novel ways of analyzing the network of competing infection pathways. The approach outlined in this study allows for the identification of new stable strains and the potential increase in disease burden from a complex systems perspective, thereby allowing for a potential response to the significant question: are the effects of a multi-demic greater than the sum of its individual viral epidemics?« less
    Free, publicly-accessible full text available September 26, 2023