Summary

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high fatality. Poor prognosis of SFTS has been associated with dysregulated host immunity; however, the immune patterns associated with pathophysiology involving SFTS exacerbation remain unclear. Here, we show that the single-cell landscape of peripheral immune responses is reprogrammed in SFTS and characterized by monocyte shift to an intermediate type along with complement activation, perturbation of plasmablast composition, and highly exhausted T cells, all correlated with lethal consequences. We identify the overexpression of interferon (IFN)-stimulated genes across most immune cell types after SFTSV infection, which are simultaneously related to older age, high viremia, and a hyperinflammatory response. A retrospective clinical study reveals no efficiency of IFN-α in treating SFTS. These data collectively support the intermediate monocytes and IFN-I-inducible plasmablasts to be major targets for SFTS virus infection, and they indicate the pivotal role of the IFN-I response in exacerbating hyperinflammation and lethal SFTS.

Overall design

We performed scRNA-seq on 27 PBMC samples from 15 SFTS patients (including four deceased and 11 surviving) and four healthy controls. A cohort study was used to identify the role of peripheral immune responses in SFTS infection. A total of 15 SFTS patients, including 11 with the CT values of RT-qPCR ranging from 25 to 30 and four with the CT values of RT-qPCR less than 25, were prospectively sampled for scRNA-seq and flow cytometry analysis.

Contributors

Hao Li†✉️, Xiaokun Li†, Shouming Lv†, Xuefang Peng†, Wei Liu✉️

Contact

lihao_1986@126.com(Hao Li), liuwei@bmi.ac.cn (Wei Liu)