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单细胞分析两名重症 COVID-19 患者揭示了与单核细胞相关且对托珠单抗有反应的细胞因子风暴。

Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm.

机构信息

Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.

Department of Hepatobiliary Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.

出版信息

Nat Commun. 2020 Aug 6;11(1):3924. doi: 10.1038/s41467-020-17834-w.

Abstract

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8 T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.

摘要

多项研究表明,针对白细胞介素-6(IL-6)受体的免疫抑制剂,包括托珠单抗,可改善感染 SARS-CoV-2 的 COVID-19 患者的致命炎症反应。在这里,我们通过对两名重症 COVID-19 患者在接受托珠单抗诱导缓解前后的免疫细胞组成进行单细胞分析,鉴定出一个单核细胞亚群,该亚群有助于炎症细胞因子风暴的发生。此外,尽管托珠单抗治疗可减轻炎症,但包括浆细胞 B 细胞和 CD8 T 细胞在内的免疫细胞仍表现出强烈的体液和细胞抗病毒免疫反应。因此,除了提供 COVID-19 多个阶段的免疫细胞分布的高维数据集外,我们的工作还深入了解了托珠单抗的治疗效果,并确定了治疗 COVID-19 相关细胞因子风暴的潜在靶细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fd1/7413381/a1050073dcfd/41467_2020_17834_Fig1_HTML.jpg

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