Higher mortality following SARS-CoV-2 infection in rural versus urban dwellers persists for two years post-infection
Document Type
Article
Publication Date
10-8-2025
Journal Title
Nature communications
MeSH Headings
Humans; COVID-19 (mortality, virology, epidemiology); Male; Female; Middle Aged; Urban Population (statistics & numerical data); Rural Population (statistics & numerical data); Retrospective Studies; SARS-CoV-2 (isolation & purification); Aged; Adult; United States (epidemiology); Aged, 80 and over; Risk Factors; Kaplan-Meier Estimate; Young Adult
Abstract
Previous studies demonstrated higher short-term mortality among rural compared with urban residents infected with SARS-CoV-2. However, whether this difference persists remains uncertain. This retrospective cohort study analyzed two-year post-COVID-19 mortality by rurality using the National Clinical Cohort Collaborative COVID-19 Enclave, a United States-based longitudinal electronic health record repository. We analyzed mortality among patients infected with SARS-CoV-2 between April 2020 and December 2022, with follow-up until December 2024. Patients were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR) groups based on residential ZIP Code. Mortality differences were assessed using Kaplan-Meier analysis and weighted multivariable Cox regression, with weights derived from demographic factors and models adjusted for background clinical risk and social vulnerability. Among 3,082,978 SARS-CoV-2-infected patients, we found a significant association between rurality and increased two-year all-cause mortality post-infection. Adjusted hazards for two-year mortality for UAR and NAR were 1.19 (95% CI 1.18-1.21) and 1.26 (1.22-1.29). A reference cohort of 4,153,216 COVID-19-negative patients showed a modest yet consistent rural mortality penalty, with a similar relative hazard across cohorts, an observed rurality-COVID-19 interaction, and a greater absolute number of deaths following SARS-CoV-2 infection. Our findings emphasize ongoing rural mortality disparities and the importance of public health efforts in rural communities.
First Page
8933
Recommended Citation
Anzalone, A Jerrod; Vest, Michael T.; Schissel, Makayla E.; Price, Bradley; Hillegass, William B.; Horswell, Ronald; Chu, San; Rosen, Clifford J.; Miele, Lucio; Santangelo, Susan L.; Smith, Gordon S.; and Hodder, Sally L., "Higher mortality following SARS-CoV-2 infection in rural versus urban dwellers persists for two years post-infection" (2025). MaineHealth Maine Medical Center. 4201.
https://knowledgeconnection.mainehealth.org/mmc/4201
