Long-term sequelae after tick-borne encephalitis in Germany: a nationwide claims-based matched cohort study

BACKGROUND: Tick-borne encephalitis (TBE) remains a public health concern in many parts of Europe despite the availability of effective vaccines. Acute disease is well described, but real-world data on the frequency, timing, and economic impact of long-term sequelae are limited. METHODS: A retrospective cohort study was performed using nationwide statutory health insurance claims covering up to 6.8 million insured individuals in Germany (2013-2023). Incident TBE cases were matched 1:5 to TBE-free controls by age, sex, region, comorbidities and healthcare utilization prior to index event. Neurological, mental, and general sequelae occurring ≥90 days after diagnosis or ≥30 days after hospital discharge (whichever came last) were assessed through 18 months. Healthcare utilization, direct medical costs, sick leave, and corresponding sickness benefit payments were compared. RESULTS: Among 187 TBE patients (mean age 44 years; 57% male) and 881 controls, neurological sequelae occurred significantly more often after TBE (incidence rate ratio 1.56, 95% CI 1.13-2.15), particularly in adults ≥40 years and in men. No significant differences were observed for general and mental sequelae. Median sequela onset was 94 days after TBE index diagnosis. Overall costs were significantly higher among TBE patients in the post-acute phase, largely attributable to excess sick-leave days (+23.3, 95% CI 8.9-37.6) and higher sickness-benefit payments. CONCLUSIONS: TBE was associated with an excess of neurological sequelae, increased sick leave, and higher sickness-benefit costs during follow-up. Although the sample size was modest and several estimates showed wide confidence intervals, the findings suggest a relevant post-acute clinical and societal burden and support the importance of follow-up care and preventive vaccination in Germany.