Immune profiling and prognosis implications in severe fever with thrombocytopenia syndrome with and without hemophagocytic lymphohistiocytosis.

OBJECTIVE

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high mortality, particularly when complicated by hemophagocytic lymphohistiocytosis (HLH). This study aimed to characterize the immunological and clinical features of SFTS patients with and without HLH, and to determine the impact of HLH on disease severity and prognosis.

METHOD: A total of 233 patients with laboratory-confirmed SFTS were enrolled, including 112 who developed HLH during hospitalization (SFTS-HLH group) and 121 with SFTS alone. Clinical, laboratory and immunological parameters were analyzed. Immune cell subsets, activation/exhaustion markers, proliferation and cytotoxicity were assessed using flow cytometry. Prognostic factors for 28-day mortality were identified using Cox proportional hazards regression.

RESULTS

SFTS-HLH patients exhibited more severe clinical manifestations, higher mortality, greater organ dysfunction and more frequency co-infections than the SFTS group. Immunologically, SFTS-HLH patients exhibited more profound lymphopenia, upregulation of exhaustion markers (PD-1, Tim-3, CD39), impaired CD8+ T cell cytotoxicity, and reduced NK cell proliferation compared with SFTS and HC groups. These abnormalities were more pronounced in non-survivors than in survivors. SFTSV RNA viral load was significantly higher in SFTS-HLH patients and correlated positively with proinflammatory cytokines and organ injury markers. Multivariate Cox analysis identified SFTS-HLH (HR = 2.942, 95 % CI: 1.277-6.775) and high viral load (HR = 1.636, 95 % CI: 1.239-2.159) as independent predictors of 28-day mortality.

CONCLUSION

SFTS complicated by HLH is characterized by immune dysregulation, high viral burden, and increased mortality. Early recognition of HLH and immune-virological surveillance may aid risk stratification and improve patient outcomes.