Single-cell landscape of peripheral immune responses to fatal SFTS

We performed scRNA-seq on 27 PBMC samples from 15 SFTS patients (including four deceased and 11 surviving) and four healthy controls. We found that the immune cell landscape was 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 were correlated with lethal consequences. We identified the overexpression of interferon-stimulated genes across most immune cell types post SFTSV infection, which were simultaneously related to older age, high viremia and hyper-inflammation. These data collectively supported the intermediate monocytes and IFN-I-inducible plasmablasts to be major targets for SFTSV infection, and proposed the pivotal role of IFN-I response in exacerbating hyper-inflammation and lethal SFTS, which might help to identify therapeutic strategies for SFTS. Overall design: 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.