BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease with high mortality, for which early risk stratification remains challenging. Soluble CD25 (sCD25), a marker of immune activation, has prognostic value in other inflammatory conditions, but its role in SFTS remains unclear. METHODS: We conducted a multicenter retrospective cohort study of 200 laboratory-confirmed SFTS patients, including a derivation cohort (n = 132) and an independent external validation cohort (n = 68). Serum sCD25 levels at admission were analyzed using Cox regression to assess mortality prediction. To explore the cellular origin of sCD25, we re-analyzed public single-cell RNA-sequencing data and performed in vitro IL-2 stimulation experiments. RESULTS: Non-survivors had significantly higher serum sCD25 levels than survivors (P < 0.001), and sCD25 independently predicted mortality (hazard ratio 1.003, P < 0.001). A prognostic model combining sCD25 and the AST/ALT ratio showed strong discrimination, with an area under the curve of 0.918 in the derivation cohort and 0.829 in external validation. Serum sCD25 levels positively correlated with viral load (r = 0.558, P = 0.011). Single-cell analysis revealed that CD25 expression was largely confined to CD4⁺ T cells, which in non-survivors displayed an interferon-stimulated gene signature and altered cell-cell communication. Consistently, serum IL-2 levels were elevated in fatal cases, and IL-2 stimulation expanded CD4⁺CD25⁺ T cells and increased sCD25 release in vitro. CONCLUSIONS: Serum sCD25 is an independent prognostic biomarker for SFTS mortality and reflects IL-2-associated dysregulation of CD4⁺CD25⁺ T cells, highlighting immune dysregulation in SFTS pathogenesis.
Zhang et al. (Thu,) studied this question.