Heterogeneity of lymphoid cells in PBMCs in the acute phase of SFTS: single-cell transcriptome profiling

Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (DBV), triggers aberrant immune activation and cytokine storm, contributing to poor prognosis, yet its immune dysfunction mechanism remains unclear. Current treatments rely on symptomatic treatment and glucocorticoids without a standardized guideline. This study investigated the mechanism of abnormal lymphocyte function in acute-phase SFTS and glucocorticoid-induced alterations in lymphoid cells using single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis. Three healthy volunteers and 13 patients in the acute phase of SFTS were enrolled in the experiment and divided into four groups. We performed scRNA-seq from the 3’ end of mRNA on peripheral blood mononuclear cells (PBMCs) samples from the 16 participants. Bioinformatics analysis was used to profile patient immunograms and elucidate subpopulation compositions, developmental trajectories, and lymphoid cell interactions. We obtained 120,886 lymphoid cells that were then divided into 23 functionally heterogeneous subsets. The result shows that severe SFTS patients had a stronger inflammatory and acquired immune response. Glucocorticoid treatment can suppress inflammation and interferon response but inhibit the production of virus-specific antibodies. These findings suggest that proper glucocorticoid administration could mitigate the hyperinflammatory state in severe SFTS cases at the acute disease stage, though it is not recommended as a conventional treatment due to potential antiviral immune suppression. This study provides insights into SFTS immunopathology and guides optimized glucocorticoid use in clinical practice.