A multiscale modeling framework for Scenario Modeling: Characterizing the heterogeneity of the COVID-19 epidemic in the US.

The Scenario Modeling Hub (SMH) initiative provides projections of potential epidemic scenarios in the United States (US) by using a multi-model approach. Our contribution to the SMH is generated by a multiscale model that combines the global epidemic metapopulation modeling approach (GLEAM) with a local epidemic and mobility model of the US (LEAM-US), first introduced here. The LEAM-US model consists of 3142 subpopulations each representing a single county across the 50 US states and the District of Columbia, enabling us to project state and national trajectories of COVID-19 cases, hospitalizations, and deaths under different epidemic scenarios. The model is age-structured, and multi-strain. It integrates data on vaccine administration, human mobility, and non-pharmaceutical interventions. The model contributed to all 17 rounds of the SMH, and allows for the mechanistic characterization of the spatio-temporal heterogeneities observed during the COVID-19 pandemic. Here we describe the mathematical and computational structure of our model, and present the results concerning the emergence of the SARS-CoV-2 Alpha variant (lineage designation B.1.1.7) as a case study. Our findings show considerable spatial and temporal heterogeneity in the introduction and diffusion of the Alpha variant, both at the level of individual states and combined statistical areas, as it competes against the ancestral lineage. We discuss the key factors driving the time required for the Alpha variant to rise to dominance within a population, and quantify the impact that the emergence of the Alpha variant had on the effective reproduction number at the state level. Overall, we show that our multiscale modeling approach is able to capture the complexity and heterogeneity of the COVID-19 pandemic response in the US.