Background
Rural regions in the U.S. have unique health challenges, including higher socioeconomic inequalities, greater comorbidity prevalence, and limited healthcare access. Previous work has demonstrated that these challenges extend to COVID-19, with rural residents having worse acute outcomes after SARS-CoV-2 infection. However, the longer-term impact of COVID-19 on rural residents remains uncertain. This study analyzed post-COVID-19 short- and long-term mortality by rural residency in a large U.S. cohort.
Methods
This retrospective cohort study utilized the National COVID Cohort Collaborative (N3C), a longitudinal EHR repository. We analyzed 2-year mortality among patients infected with SARS-CoV-2 between April 2020 and June 2022, with follow-up until June 2024. Patients were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR) groups based on residential ZIP codes using Rural-Urban Commuting Area codes. Mortality differences were assessed using Kaplan-Meier analysis and weighted multivariable Cox regression, adjusting for demographic differences and background risk, including obesity, hypertension, substance use, tobacco use, individual comorbid conditions included in the Charlson Comorbidity Index, COVID-19 vaccination status, residential social vulnerability (independent of rural residency using the CDC’s Social Vulnerability Index), U.S. Census Division, and SARS-CoV-2 variant-dominant strain at the time of infection.
Results
Among 2,658,202 SARS-CoV-2-infected patients, Kaplan-Meier curves revealed a significant association between rurality and 2-year mortality post-infection (p<0.001). Cox regression exhibited higher mortality among rural residents at 1-, 3-, 12-, and 24-months post-infection (Figure 1). Compared to urban dwellers, the adjusted hazard ratios for 2-year mortality for UAR and NAR were 1.27 (1.25-1.28) and 1.31 (1.30-1.32).
Conclusions
We demonstrated that rural dwellers have significantly higher mortality than urban dwellers after SARS-CoV-2 infection, and this worse prognosis persists for at least 2 years, with an approximate 27% increased risk of 2-year all-cause mortality risk for rural-dwelling patients following COVID-19, even after adjusting for background risk and demographic differences. The COVID-19-exacerbated rural mortality penalty persists beyond the immediate acute period after infection, highlighting a need for continued public health prioritization of rural communities.
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