T Follicular Helper Cell Immune Signatures Associated With Disease Severity in Severe Fever With Thrombocytopenia...

Severe fever with thrombocytopenia syndrome (SFTS) is marked by high case fatality and profound antiviral immune dysregulation, yet the clinical implications of changes in circulating T follicular helper (Tfh) cells remain unclear.

We enrolled 79 patients with RT-PCR-confirmed SFTSV infection who were hospitalized from May to October 2023 and categorized them as acute-phase survivors (AS) or acute-phase deceased (AD). Frequencies of circulating Tfh subsets (Tfh1, Tfh2, Tfh17, and PD-1⁺ Tfh) were measured by flow cytometry, and plasma SFTSV RNA was quantified by RT-qPCR. Their relationships with clinical variables and prognosis were analyzed using correlation analysis, ROC analysis, Kaplan-Meier survival analysis, and forward-selection multivariable logistic regression.

Compared with survivors, patients in the AD group showed greater inflammatory activation, more pronounced coagulation disturbances, and higher plasma viral loads. While overall circulating Tfh frequencies were elevated in AD patients, subset profiling demonstrated a clear bias toward Tfh2 expansion together with contraction of Tfh1 and Tfh17 populations. Among these subsets, Tfh2 had the best discriminatory value for mortality (AUC = 0.724). Lower Tfh1 and Tfh17 frequencies were associated with poorer 28-day survival. Viral RNA levels were positively related to total Tfh and Tfh2 frequencies and negatively related to Tfh17. After adjustment for age, HLH status, and viral load, Tfh1 remained an independent correlate of acute-phase mortality.

Acute SFTSV infection is associated with substantial remodeling of the circulating Tfh compartment. Expansion of Tfh2 alongside reduction of Tfh1 and Tfh17 was linked to heavier viral burden and worse clinical outcome. The independent association between lower Tfh1 frequency and mortality suggests that Tfh profiling may be useful for early risk assessment and offers mechanistic insight into defective humoral immunity in severe SFTS.