Metabolic Profiling Reveals Prognostic Biomarkers for SFTS: Insights into Disease Severity and Clinical Outcomes

Severe fever with thrombocytopenia syndrome (SFTS) is a viral infection primarily found in Asia, with a case fatality rate of about 10%. Despite its increasing prevalence, the underlying pathogenic mechanisms remain poorly understood, limiting the development of effective therapeutic interventions. We employed an untargeted metabolomics approach using liquid chromatography-mass spectrometry (LC-MS) to analyze serum samples from 78 SFTS patients during the acute phase of their illness. Differential metabolic features between survival and fatal cases were identified through multivariate statistical analyses. Furthermore, we constructed a metabolic prognostic model based on these biomarkers to predict disease severity. Significant alterations were observed in four key metabolic pathways: sphingolipid metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, primary bile acid biosynthesis, and phenylalanine metabolism. Elevated levels of phenylacetic acid and isocitric acid were strongly associated with adverse outcomes and demonstrated high discriminatory power in distinguishing fatal cases from survivors. The metabolic prognostic model incorporating these biomarkers achieved a sensitivity of 75% and a specificity of 90% in predicting disease severity. Our findings highlight the pivotal role of metabolic dysregulation in the pathogenesis of SFTS and suggest that targeting specific metabolic pathways could open new avenues for therapeutic development. The identification of prognostic biomarkers provides a valuable tool for early risk stratification and timely clinical intervention, potentially improving patient outcomes.