Lactate Dehydrogenase-to-Lymphocyte Ratio Predicts Early Mortality in Patients with Severe Fever with Thrombocytopenia Syndrome

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV) with high mortality. MethodsBetween January 2022 and October 2024, a total of 208 cases from Yantai Qishan Hospital have been included in this study. The sLLR was defined as the standardized ratio of lactate dehydrogenase to absolute lymphocyte count. Firth penalized regression was utilized for variable selection. The receiver operating characteristic (ROC) analysis compared sLLR with C-reactive protein/albumin ratio (CAR). A nomogram based on sLLR was validated through 1,000 bootstraps. Performance was assessed using AUC, Brier score, and decision curve analysis (DCA). ResultsNon-survivors had a higher sLLR level (median 2.88 vs. 1.15; P<0.001). sLLR showed superior discrimination compared to CAR (AUC 0.804 vs. 0.648, P=0.016), with 95.7% sensitivity. The nomogram achieved AUC 0.87 (95%CI 0.798-0.942) and validation AUC 0.876 (Brier score 0.074; Hosmer-Lemeshow P=0.778). ConclusionssLLR can be utilized as an independent prognostic factor for SFTS patients. The nomogram enables rapid mortality risk stratification, providing a practical tool for frontline clinicians in resource-limited settings. SynopsisThis study identifies the standardized lactate dehydrogenase-to-lymphocyte ratio (sLLR) as a novel prognostic biomarker for early mortality in patients with Severe Fever with Thrombocytopenia Syndrome (SFTS). Through a retrospective cohort of 208 laboratory-confirmed SFTS cases, non-survivors exhibited significantly higher sLLR levels (median 2.88 vs. 1.15, P<0.001) compared to survivors. The sLLR demonstrated superior discriminatory power (AUC 0.804) over the established C-reactive protein/albumin ratio (CAR; AUC 0.648, P=0.016), with 95.7% sensitivity at a cutoff of 1.457. Multivariate Firth penalized regression confirmed sLLR as an independent predictor of mortality (OR=1.84, 95% CI 1.15-3.06; P=0.012), alongside neurological manifestations (OR=4.25). A clinically practical nomogram integrating sLLR, activated partial thromboplastin time (APTT), and neurological symptoms achieved robust performance (AUC 0.876 after 1,000 bootstraps) and calibration (Brier score 0.074), enabling rapid risk stratification in resource-limited settings. These findings illuminate sLLRs pathophysiological relevance--reflecting virally driven tissue damage (elevated LDH) and immune depletion (lymphocytopenia)--and provide a tool to guide early intervention for high-risk SFTS patients.