《Nature,3月6日,Dynamic blood single-cell immune responses in patients with COVID-19》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangmin
  • 发布时间:2021-03-09
  • Dynamic blood single-cell immune responses in patients with COVID-19

    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

    Signal Transduction and Targeted Therapy volume 6, Article number: 110 (2021)

    Abstract

    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 interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

  • 原文来源:https://www.nature.com/articles/s41392-021-00526-2
相关报告
  • 《Nature,6月8日,A single-cell atlas of the peripheral immune response in patients with severe COVID-19》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-06-09
    • A single-cell atlas of the peripheral immune response in patients with severe COVID-19 Aaron J. Wilk, Arjun Rustagi, Nancy Q. Zhao, Jonasel Roque, Giovanny J. Martínez-Colón, Julia L. McKechnie, Geoffrey T. Ivison, Thanmayi Ranganath, Rosemary Vergara, Taylor Hollis, Laura J. Simpson, Philip Grant, Aruna Subramanian, Angela J. Rogers & Catherine A. Blish Nature Medicine (2020) Abstract There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.
  • 《Nature,5月4日,Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-05-05
    • Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing Wen Wen, Wenru Su, Hao Tang, Wenqing Le, Xiaopeng Zhang, Yingfeng Zheng, Xiuxing Liu, Lihui Xie, Jianmin Li, Jinguo Ye, Liwei Dong, Xiuliang Cui, Yushan Miao, Depeng Wang, Jiantao Dong, Chuanle Xiao, Wei Chen & Hongyang Wang Cell Discovery volume 6, Article number: 31 (2020) Abstract COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1β+ monocytes in the ERS. CD4+ T cells and CD8+ T cells decreased significantly and expressed high levels of inflammatory genes in the ERS.