Neurological Manifestations and High Viral Load as Independent Predictors of Mortality in Severe Fever With Thrombocytopenia Syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral hemorrhagic fever, is characterized by high mortality rates. While neurological complications (eg, seizures, encephalitis) have been identified as adverse prognostic factors in severe cases, their association with viral replication, immune responses, and neuroinflammation remain poorly defined and urgently require systematic investigation. Method: A cohort of 277 patients with SFTS was included and stratified based on neurological symptoms. Clinical characteristics, laboratory results, and immune markers were compared between groups. Results: Neurological symptoms developed in 78 (28.2%) patients and were associated with significantly higher 28-day mortality. These patients had higher viral loads, elevated inflammatory cytokines (IL-6, IL-10, TNF-α, and ferritin), and more severe multi-organ dysfunction. Compared with survivors, nonsurvivors showed reduced platelet and T-cell counts, and disregulated B-cell subsets with increased plasmablasts and double-negative B cells. Viral load correlated with cytokine elevation, coagulopathy (prolonged APTT), and renal impairment (reduced eGFR). Multivariate Cox proportional hazards regression identified neurological symptoms (HR = 2.565; 95% CI: 1.641-4.011; Conclusions: Neurological manifestations and elevated viral load play a central role in the progression of SFTS and are closely associated with adverse clinical outcomes. Considering neurological symptoms and immune profiles in prognostic assessments may improve early recognition of high-risk patients and inform clinical management.