Rural–Urban Disparities in COVID-19 Vaccine Uptake and Associated Mortality and Cardiovascular Disease Outcomes in the United States

Background: The COVID-19 pandemic magnified long-standing health disparities in the United States, particularly among rural, disadvantaged populations. These communities experience greater barriers to healthcare access, a higher prevalence of chronic illness, and increased vaccine hesitancy factors that collectively contribute to poorer health outcomes. Methods: This narrative review examines rural–urban disparities in COVID-19 vaccine uptake and their impact on mortality, with a focus on cardiovascular disease (CVD) outcomes. We synthesized the peer-reviewed literature, CDC data, and U.S. Census reports to assess factors contributing to vaccine hesitancy, vaccination coverage, COVID-19-related mortality, and CVD mortality trends. Results: Rural residents were less likely to initiate COVID-19 vaccination, showed greater vaccine hesitancy, and experienced higher rates of both COVID-19 and CVD mortality. These disparities were further driven by safety concerns surrounding mRNA technology, misinformation, infrastructural barriers, and sociodemographic factors including political affiliation, education, poverty, and religion. Notably, pre-existing CVD increased vulnerability to severe COVID-19 outcomes in rural communities. Conclusions: Expanding vaccination efforts and improving healthcare infrastructure are essential for addressing these widening health inequities. Future public health strategies should prioritize culturally tailored interventions and rural-specific outreach to reduce vaccine hesitancy and improve mortality outcomes in underserved populations.