Abstract
Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (DBV), triggers aberrant immune activation and cytokine storms, contributing to poor prognosis; however, its immune dysfunction mechanism remains unclear. Current management relies on symptomatic treatment and glucocorticoids, but no standardized treatment guidelines exist. This study investigated the mechanisms of abnormal lymphocyte function in acute-phase SFTS and the effects of glucocorticoid treatment on lymphoid cells using single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis. We enrolled three healthy volunteers and 13 patients with acute SFTS and divided them into four groups. ScRNA-seq was performed on peripheral blood mononuclear cells from all 16 participants, capturing transcripts from the 3' ends of mRNA. Bioinformatics analyses were used to profile patient immunological signatures, characterize subpopulation compositions, infer developmental trajectories, and assess lymphoid cell interactions. We obtained 120886 lymphoid cells, which were clustered into 23 functionally heterogeneous subsets. Results showed that patients with severe SFTS exhibited stronger inflammatory and adaptive immune responses. Glucocorticoid treatment suppressed inflammation and the interferon response but also inhibited the production of virus-specific antibodies. These findings suggest that appropriate glucocorticoid administration may alleviate the hyperinflammatory state in severe SFTS during the acute phase, although it is not recommended as a conventional treatment because of its potential to suppress antiviral immunity. This study provides insights into SFTS immunopathology and informs the optimized clinical use of glucocorticoids.