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Purpose: To quantify and compare SARS-CoV-2 transmission potential across Alabama, Louisiana, and Mississippi and selected counties.Methods: To determine the time-varying reproduction number Rt of SARS-CoV-2, we applied the R package EpiEstim to the time series of daily incidence of confirmed cases (mid-March 2020 - May 17, 2021) shifted backward by 9 days. Median Rt percentage change when policies changed was determined. Linear regression was performed between log10-transformed cumulative incidence and log10-transformed population size at four time points.Results: Stay-at-home orders, face mask mandates, and vaccinations were associated with the most significant reductions in SARS-CoV-2 transmission in the three southern states. Rt across the three states decreased significantly by ≥20% following stay-at-home orders. We observed varying degrees of reductions in Rt across states following other policies. Rural Alabama counties experienced higher per capita cumulative cases relative to urban ones as of June 17 and October 17, 2020. Meanwhile, Louisiana and Mississippi saw the disproportionate impact of SARS-CoV-2 in rural counties compared to urban ones throughout the study period.Conclusion: State and county policies had an impact on local pandemic trajectories. The rural-urban disparities in case burden call for evidence-based approaches in tailoring health promotion interventions and vaccination campaigns to rural residents. [ABSTRACT FROM AUTHOR]