AUTHOR=Bao Yida , Huang Iris , Li Qi , Zhang Zheng , Xing Yuan , Hou Dongfang , Ye Jiafeng TITLE=A framework for modeling county-level COVID-19 transmission JOURNAL=Frontiers in Public Health VOLUME=Volume 13 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1608360 DOI=10.3389/fpubh.2025.1608360 ISSN=2296-2565 ABSTRACT=This study examines COVID-19 transmission across 3,142 U.S. counties using a truncated dataset from March to September 2020. County-level factors include demographics, socioeconomic status, environmental conditions, and mobility patterns. Ordinary Least Squares regression establishes a baseline for analyzing COVID-19 confirm case counts for each county. We then use Moran's I to evaluate spatial clustering, prompting Spatial Autoregressive and Spatial Error Models when autocorrelation is significant. Notably, spatial models outperform the Ordinary Least Squares approach—R2 rises from 0.4849 with Ordinary Least Squares to 0.6846 under Spatial Error Model, while RMSE decreases from 2.0891 to 1.642—demonstrating improved fit and more accurate spatial transmission dynamics. A multilevel framework further explores state-level policy variations. Finally, Geographically Weighted Regression captures spatial non-stationarity by mapping local coefficient differences; we visualized temperature, precipitation, and other key variables—revealing precipitation peaks near 110° W in the Southeast and Northeast and strong sensitivity to temperature. This integrated sequence of methods provides a comprehensive lens for studying epidemiological phenomena. While certain findings align with established research, other variables reveal unexpected patterns. The proposed framework offers a robust template for future investigations where spatial dependence and policy heterogeneity warrant close examination.