Long-Term Mortality Following SARS-CoV-2 Infection in Rural Versus Urban Dwellers with Autoimmune or Inflammatory Rheumatic Disease (AIRD): A Retrospective Cohort Analysis from the National COVID Cohort Collaborative (N3C).

ABSTRACT

OBJECTIVE: Autoimmune or inflammatory rheumatic diseases (AIRD) increase the risk for poor COVID-19 outcomes. While rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to 2 years post-infection, among people with AIRD using a large, nationally sampled U.S. METHODS: This retrospective study utilized the National COVID Cohort Collaborative, a medical-records repository containing COVID-19 patient data. We included adults with ≥2 AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential ZIP Codes. We adjusted for AIRD medications and glucocorticoid usage, age, sex, race and ethnicity, tobacco/substance usage, comorbid burden, and SARS-CoV-2 variant-dominant periods. Multivariable Cox Proportional Hazards with inverse probability treatment weighting assessed associations between rurality and 2-year, all-cause mortality. RESULTS: Among the 86,467 SARS-CoV-2-infected persons with AIRD, we observed a higher risk for 2-year post-COVID-19 mortality in rural versus urban dwellers. Rural-residing persons with AIRD had higher 2-year, all-cause mortality risk (aHR 1.24, 95% CI 1.19-1.29). Use of glucocorticoids, immunosuppressives, and rituximab was associated with a higher risk for 2-year post-COVID-19 mortality, while risk with non-biologic or biologic DMARDs was lower. CONCLUSION: Rural residence in people with AIRD was independently associated with higher post-COVID-19 2-year mortality in a large U.S. cohort after adjusting for background risk factors. Policymakers and healthcare providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS-CoV-2 infection, especially among higher-risk rural residents.