Characterizing US Spatial Connectivity and Implications for Geographical Disease Dynamics and Metapopulation Modeling: Longitudinal Observational Study.

Background: Human mobility is expected to be a critical factor in the geographic diffusion of infectious diseases, and this assumption led to the implementation of social distancing policies during the early fight against the COVID-19 emergency in the United States. Yet, because of substantial data gaps in the past, what still eludes our understanding are the following questions: (1) How does mobility contribute to the spread of infection within the United States at local, regional, and national scales? (2) How do seasonality and shifts in behavior affect mobility over time? (3) At what geographic level is mobility homogeneous across the United States? Objective: This study aimed to address the questions that are critical for developing accurate transmission models, predicting the spatial propagation of disease across scales, and understanding the optimal geographical and temporal scale for the implementation of control policies. Methods: We analyzed high-resolution mobility data from mobile app usage from SafeGraph Inc, mapping daily connectivity between the US counties to grasp spatial clustering and temporal stability. Integrating this into a spatially explicit transmission model, we replicated SARS-CoV-2's first wave invasion, assessing mobility's spatiotemporal impact on disease predictions. Results: Analysis from 2019 to 2021 showed that mobility patterns remained stable, except for a decline in April 2020 due to lockdowns, which reduced daily movements from 45 million to approximately 25 million nationwide. Despite this reduction, intercounty connectivity remained seasonally stable, largely unaffected during the early COVID-19 phase, with a median Spearman coefficient of 0.62 (SD 0.01) between daily connectivity and gravity networks., We identified 104 geographic clusters of US counties with strong internal mobility connectivity and weaker links to counties outside these clusters. These clusters were stable over time, largely overlapping state boundaries (normalized mutual information=0.82) and demonstrating high temporal stability (normalized mutual information=0.95). Our findings suggest that intercounty connectivity is relatively static and homogeneous at the substate level. Furthermore, while county-level, daily mobility data best captures disease invasion, static mobility data aggregated to the cluster level also effectively models spatial diffusion. Conclusions: Our work demonstrates that intercounty mobility was negligibly affected outside the lockdown period in April 2020, explaining the broad spatial distribution of COVID-19 outbreaks in the United States during the early phase of the pandemic. Such geographically dispersed outbreaks place a significant strain on national public health resources and necessitate complex metapopulation modeling approaches for predicting disease dynamics and control design. We thus inform the design of such metapopulation models to balance high disease predictability with low data requirements.