Abstract
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, characterized by cytokine storm and immune suppression. The interleukin-6-to-lymphocyte ratio (IL-6/LY) has demonstrated prognostic value in viral infections with dysregulated host immune responses. This study aimed to evaluate the prognostic value of IL-6/LY for early mortality in patients with SFTS. METHODS: This multicenter cohort included 323 patients at Yantai Qishan Hospital (January 2022-December 2024) as the training cohort and 172 patients at Qingdao No. 6 People's Hospital (January 2023-October 2025) as the validation cohort. Univariable and multivariable logistic regression identified independent predictors of mortality. Prognostic performance was assessed using the area under the receiver operating characteristic (ROC) curve, and clinical benefit was evaluated by decision curve analysis (DCA). Survival was analyzed using the Kaplan-Meier method with the log-rank test. RESULTS: A total of 495 patients were included in the study, with mortality rate of 21.21% (105/495). Multivariate logistic regression analysis identified DBV RNA level, age, and IL-6/LY as independent predictors of fatal outcome in SFTS. Compared with other predictors, IL-6/LY showed the strongest predictive performance for mortality in the training cohort (AUC = 0.839, 95% CI: 0.792-0.886; P < 0.001) and was externally validated with excellent discrimination (AUC = 0.812, 95% CI: 0.735-0.890; P < 0.001). Patients with elevated IL-6/LY levels (≥ 1.77) had a significantly lower survival probability than those with lower IL-6/LY (log-rank P < 0.001). DCA demonstrated great clinical benefit for IL-6/LY in both the training and external validation cohorts. CONCLUSION: IL-6/LY as a novel marker associated with immune dysregulation shows strong independent prognostic value for mortality in SFTS.