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

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.

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Publication Details

Journal
Nature Communications
Published
2025-10-08
DOI
https://doi.org/10.1038/s41467-025-63944-8
Citations
3
Primary Topic
COVID-19 and healthcare impacts
Type
article
Field-Weighted Citation Impact
3.14

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article

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

Ronald Horswell, Gordon S. Smith, William B. Hillegass, Sally Hodder et al.
3 citations
Nature Communications
COVID-19 and healthcare impacts
3.14
article

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

Ronald Horswell, Gordon S. Smith, William B. Hillegass, Sally Hodder, Lucio Miele, Clifford J. Rosen, Alfred Jerrod Anzalone, Christopher G. Chute, Michael T. Vest, Bradley S. Price, Makayla Schissel, San Chu, Susan L. Santangelo
article en
3 citations

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.

Nature CommunicationsVol. 16(1)
Pennington Biomedical Research Center (US), West Virginia University (US), Tufts University (US), Christiana Care Health System (US), Nebraska Medical Center (US), Johns Hopkins University (US), Jackson Memorial Hospital (US), University of Mississippi Medical Center (US), MaineHealth (US), University of Nebraska Medical Center (US), Louisiana State University Health Sciences Center New Orleans (US)
Bill and Melinda Gates Foundation, Yale University, University of Southern California, Brown University, Children's Hospital of Philadelphia, University of Nebraska Medical Center, Vanderbilt University, University of Miami, University of Pennsylvania, Ohio State University, Emory University, Tufts Medical Center, NYU Langone Medical Center, University of Wisconsin-Madison, Northwestern University, George Washington University, Wake Forest University, Cincinnati Children's Hospital Medical Center, Children's Hospital Colorado, Vanderbilt Institute for Clinical and Translational Research, University of Chicago, University of Minnesota, Washington University in St. Louis, University of Michigan, Harvard Catalyst, Loyola University Chicago, University of Utah, University of Washington, University of Texas Medical Branch, Tulane University, Johns Hopkins University, University of Pittsburgh, University of Oklahoma, Institute for Translational Medicine and Therapeutics, Institute of Clinical and Translational Sciences, Georgetown University, University of Rochester, University of Cincinnati, Case Western Reserve University, Dartmouth College, Pennsylvania State University, Carilion Clinic, Rush University, University of South Carolina, Virginia Commonwealth University, Southern California Clinical and Translational Science Institute, West Virginia University, Montana State University, Rutgers, The State University of New Jersey, MedStar Health Research Institute, Georgetown-Howard Universities Center for Clinical and Translational Science, University of Texas Health Science Center at Houston, NorthShore University HealthSystem, Vanderbilt University Medical Center, Institute of Translational Health Sciences, Georgia Clinical and Translational Science Alliance, Penn State Clinical and Translational Science Institute, Children's National Hospital, Louisiana Clinical and Translational Science Center, Ochsner Health, West Virginia Clinical and Translational Science Institute, Stony Brook University, National Institutes of Health, University of Illinois at Urbana-Champaign, Institute for Clinical and Translational Research, University of Wisconsin, Madison, University of California, Los Angeles, Weill Cornell Medical College, University of California, Davis, Oregon Clinical and Translational Research Institute, University of North Carolina at Chapel Hill, University of California, San Diego, University of Oklahoma Health Sciences Center, University of California, San Francisco, Michigan Institute for Clinical and Health Research, University of Texas Health Science Center at San Antonio, University of California, Irvine, Leonard M. Miller School of Medicine, Center for Clinical and Translational Research, School of Medicine, Indiana University, Center for Clinical and Translational Science, University of Massachusetts, Center for Clinical and Translational Science, Mayo Clinic, Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Irving Medical Center, Columbia University, Translational Research Institute, University of Arkansas for Medical Sciences, South Carolina Clinical and Translational Research Institute, Medical University of South Carolina, Clinical and Translational Science Institute, University of Florida, Clinical and Translational Science Institute, Boston University, Frontiers Clinical and Translational Science Institute, University of Kansas, Clinical and Translational Science Center, University of New Mexico, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences, Institute for Integration of Medicine and Science, Colorado Clinical and Translational Sciences Institute, Yale Center for Clinical Investigation, Yale School of Medicine, Institute for Clinical and Translational Science, University of California, Irvine, Wake Forest Clinical and Translational Science Institute, Wake Forest School of Medicine, Accelerated Innovation Research Initiative Turning Top Science and Ideas into High-Impact Values
Openalex Percentile: Top 7%
COVID-19 and healthcare impacts
3.14
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