Targeted organic acid profiling in Crimean-Congo hemorrhagic fever: A metabolomics-based approach to biomarker discovery.

Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral infection associated with high morbidity and mortality. Understanding the metabolic alterations associated with the disease may uncover novel biomarkers for diagnosis and disease severity assessment. In this study, we conducted a targeted metabolomic analysis using LC-MS/MS to quantify serum organic acid levels in 115 CCHF-positive patients, 30 CCHF-negative patients, and 45 healthy controls. This is the first study to comprehensively profile organic acid alterations in CCHFV using targeted metabolomics. Our findings revealed that several organic acids, notably alpha-ketoglutaric acid, malic acid, p-hydroxyphenyllactic acid, and 3-hydroxyisobutyric acid, were significantly elevated in CCHFV patients and positively correlated with markers of inflammation and coagulation. These metabolites demonstrated strong prognostic performance for intensive care unit (ICU) admission. Additionally, survival analysis indicated that elevated levels of specific organic acids were associated with increased mortality risk. Pathway enrichment analysis identified dysregulation of the TCA cycle, pyruvate metabolism, and amino acid pathways in CCHF patients. Our results suggest that specific organic acids may serve as novel biomarkers for disease severity and prognosis, offering potential tools for early risk stratification and improved clinical management of CCHF.