Single-cell landscape of immunological responses in COVID-19 patients

Zhang, Ji-Yuan; Wang, Xiang-Ming; Xing, Xudong; Xu, Zhe; Zhang, Chao; Song, Jin-Wen; Fan, Xing; Xia, Peng; Fu, Jun-Liang; Wang, Si-Yu; Xu, Ruo-Nan; Dai, Xiao-Peng; Shi, Lei; Huang, Lei; Jiang, Tian-Jun; Shi, Ming; Zhang, Yuxia; Zumla, Alimuddin; Maeurer, Markus; Bai, Fan; Wang, Fu-Sheng

In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.