Higher mortality following SARS-CoV-2 infection in rural versus urban dwellers persists for two years post-infection

Authors

A. Jerrod Anzalone, University of Nebraska, Omaha, NE
Michael T. Vest, Christiana Care Health System, Newark, DE
Makayla E. Schissel, University of Nebraska, Omaha, NE
Bradley Price, West Virginia University, Morgantown, WV
William B. Hillegass, University of Mississippi, Jackson, MS
Ronald Horswell, Pennington Biomedical Research Center, Baton Rouge, LA
San Chu, Pennington Biomedical Research Center, Baton Rouge, LA
Clifford J. Rosen, MaineHealth Institute for Research, Scarborough, ME
Lucio Miele, LSU Health Sciences Center - New OrleansFollow
Susan L. Santangelo, MaineHealth Institute for Research, Scarborough, ME
Gordon S. Smith, West Virginia University, Morgantown, WV
Sally L. Hodder, West Virginia University, Morgantown, WV
Christopher G. Chute, Johns Hopkins University, Baltimore, MD

Document Type

Article

Publication Date

10-8-2025

Publication Title

Nature Communications

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.

PubMed ID

41062502

Volume

16

Issue

1

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

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.; Hodder, Sally L.; and Chute, Christopher G., "Higher mortality following SARS-CoV-2 infection in rural versus urban dwellers persists for two years post-infection" (2025). School of Medicine Faculty Publications. 4200.
https://digitalscholar.lsuhsc.edu/som_facpubs/4200
10.1038/s41467-025-63944-8