Abstract
IMPORTANCE: Aspergillosis is an under-recognized fungal infection associated with rising hospitalizations, concerns about antifungal resistance, and substantial morbidity and mortality in the U.S. Yet, national data on aspergillosis remain fragmented due to absence of centralized surveillance. OBJECTIVE: To examine demographic and geographic variation and temporal trends in aspergillosis prevalence in the U.S. from 2013 to 2023; to assess how the COVID-19 pandemic influenced prevalence across population subgroups. DESIGN: Retrospective cohort study using a large, national electronic health record (EHR) database. SETTING: 142 healthcare systems in the U.S. using Oracle Health EHR systems, encompassing disparate care settings. PARTICIPANTS: Adults aged 18 years and older who received care between January 1, 2013, and December 31, 2023. The cohort included over 76 million patients, and over 127 million person-years, with 20,764 aspergillosis diagnoses. EXPOSURES: Calendar year, patient characteristics (age, sex, race, ethnicity, residence type), and state of residence. COVID-19 was treated as a time-varying exposure. MAIN OUTCOMES AND MEASURES: Annual and overall prevalence of aspergillosis per 100,000 person-years; adjusted prevalence ratios (aPRs) by demographic group and state, estimated using quasi-Poisson and Bayesian spatiotemporal regression. COVID-19-related shifts in prevalence were assessed using estimated marginal means. RESULTS: Between 2013 and 2023, aspergillosis prevalence increased 5% annually, peaking in 2022. Rhode Island had the highest aPR across all years; Utah the lowest. Prevalence was higher in males (aPR: 1.37), older adults (aPR for ≥65 vs. 18 to 34: 4.95), and urban residents (rural aPR: 0.86). Post-COVID-19, prevalence increased disproportionately among Hispanic or Latino patients and several racial minority groups. Suggestive trends of increasing prevalence were also observed among rural residents. CONCLUSIONS AND RELEVANCE: This study provides the most comprehensive national assessment to date of aspergillosis patterns in the U.S., revealing evidence of rising prevalence and emerging disparities shaped by the COVID-19 pandemic. Clinicians should consider regional and demographic risk patterns to support earlier diagnosis, guide antifungal treatment, and improve outcomes-especially among older adults and populations disproportionately affected by COVID-19. Clinicians practicing in rural or underserved areas should be particularly mindful of shifting risk profiles and advocate for improved diagnostic resources to reduce delays in care.