Single-cell landscape of peripheral immune responses to fatal SFTS

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 in SFTS exacerbation remains unclear. Here we show the single-cell landscape of peripheral immune responses is reprogrammed in SFTS and characterized by monocyte shift to intermediate type along with complement activation, perturbation of plasmablasts composition, and highly exhausted T cells, all are correlated with lethal consequences. We identify the overexpression of interferon-stimulated genes across most immune cell types post SFTSV infection, which are simultaneously related to older age, high viremia and hyper-inflammation response. A retrospectively clinical study revealed 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 SFTSV infection, and propose the pivotal role of IFN-I response in exacerbating hyper-inflammation and lethal SFTS.