Dynamic blood single-cell immune responses in patients with COVID-19

作者：Lulin Huang, Yi Shi, Bo Gong, Li Jiang, Zhixin Zhang, Xiaoqi Liu, Jialiang Yang, Yongquan He, Zhilin Jiang, Ling Zhong, Juan Tang, Chunfang You, Qi Jiang, Bo Long, Tao Zeng, Mei Luo, Fanwei Zeng, Fanxin Zeng, Shuqiang Wang, Xingxiang Yang, Zhenglin Yang · 发表于：Signal Transduction and Targeted Therapy · 年份：2021 · DOI：10.1038/s41392-021-00526-2 · 被引用次数：127 · 研究领域：COVID-19 Clinical Research Studies、SARS-CoV-2 and COVID-19 Research、Extracellular vesicles in disease

The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of int...