Abstract
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening zoonotic disease characterized by high morbidity and mortality. The aim of this study was to investigate the associations between serum cytokine levels and clinical outcomes in SFTS patients across different age groups to obtain deeper insights into disease pathogenesis. METHODS: A total of 807 SFTS patients were enrolled in this two-center cohort study from January 2021 to December 2023. Serum samples from 78 of these patients were analyzed to determine the levels of 48 cytokines via the Luminex 200 platform. Patients were stratified by age and clinical outcome, and cytokine levels were compared across groups. RESULTS: This study included 807 SFTS patients with an average age of 63.65 ± 10.63 years. Receiver operating characteristic (ROC) curve analysis was performed in the training cohort to evaluate the ability of age to predict clinical outcomes, and 66.5 years was identified as the optimal cutoff value (AUC 0.780, 95% CI 0.741-0.818). Based on this cutoff value and clinical outcomes, the 78 patients were stratified into four groups: older survivors, older non-survivors, younger survivors, and younger non-survivors. In this limited cohort, no significant differences in cytokine levels were observed between older and younger non-survivors, nor between older and younger survivors (FDR-adjusted q > 0.05). However, multiple cytokines were significantly elevated in non-survivors compared with survivors across age strata (q < 0.05), including representative cytokines such as IL-1β, IL-6, IL-10, IFN-γ, MCP-1, and MCP-3. CONCLUSION: Cytokine levels were associated with clinical outcomes in patients with SFTS. These findings suggest that cytokine profiles may serve as potential biomarkers reflecting disease severity. Early identification of high-risk patients and the exploration of cytokine-targeted therapies warrant further investigation. CLINICAL TRIAL NUMBER: Not applicable.