Abstract
Background: Herpes zoster (HZ), resulting from the reactivation of latent varicella-zoster virus, has been increasingly observed in individuals following COVID-19. Given the shared immunological disturbances between the two conditions, this study aimed to investigate whether HZ following COVID-19 is associated with an elevated risk of renal, infectious, and autoimmune complications. Methods: This retrospective cohort study utilized data from the TriNetX global federated health network, encompassing over 9 million adults diagnosed with COVID-19 between January 2020 and January 2022. Patients who developed HZ within one year following COVID-19 diagnosis were compared to 1:1 propensity score-matched controls without HZ. Time-to-event analyses over a three-year follow-up period were conducted to estimate the risks of major adverse kidney events (MAKE; defined as acute kidney injury, dialysis dependence, or severely reduced kidney function with eGFR <30 mL/min/1.73 m(2)), sepsis, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), using Kaplan-Meier survival curves and Cox proportional hazards models. Results: HZ following COVID-19 was significantly associated with increased risks of all four outcomes: MAKE (HR 1.940, 95% CI: 1.866-2.017), sepsis (HR 2.362, 95% CI: 2.250-2.479), SLE (HR 2.667, 95% CI: 2.254-3.156), and RA (HR 2.484, 95% CI: 2.267-2.730). Subgroup analyses identified older age, diabetes, impaired renal function, and elevated inflammatory markers as key risk-enhancing factors. Conclusions: HZ following COVID-19 may serve as a clinical indicator of systemic immune dysregulation and is independently associated with increased long-term risks of renal, infectious, and autoimmune sequelae. Enhanced monitoring of this high-risk population is warranted.