Early warning indicators for severe hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) remains a significant public health concern, and early identification of severe cases is critical for improving outcomes. This review synthesizes recent advances in early warning indicators for severe HFRS. Clinically accessible indicators form the basis of early risk stratification. Key bedside signs such as high fever, severe gastrointestinal symptoms, altered mental status, and overt bleeding tendency, together with routine laboratory parameters including thrombocytopenia, leukocytosis, and elevated procalcitonin, have consistently shown robust predictive value for disease severity and mortality. Immunological markers provide mechanistic insight that also supports early identification of severe HFRS, as reflected by a core cytokine imbalance, impaired antigen-specific T- and B-cell responses, and aberrant activation of monocytes, neutrophils, and the complement system. Emerging biomarkers of endothelial barrier disruption, early renal tubular injury, oxidative stress, and metabolic dysregulation may further enhance predictive capacity. Despite these advances, challenges remain regarding external validation and clinical translation. Future research should focus on establishing standardized, multicenter-validated early warning systems to enable precise management of severe HFRS.