COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas.

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Date: Apr. 1, 2021
From: Cell(Vol. 184, Issue 7)
Publisher: Elsevier B.V.
Document Type: Report
Length: 1,251 words

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Abstract :

Keywords COVID-19; SARS-CoV-2; single-cell RNA-seq; single-cell transcriptomics; host cell range; cell-cell interaction; B cell receptor sequencing; T cell receptor sequencing; cytokine storm; ligand-receptor interaction Highlights * Detailed COVID-19 immune landscape depicted by integrated 1.46 million single cells * Peripheral immune subtypes differentially associated with distinct clinical features * SARS-CoV-2 RNA is present in diverse epithelial and immune cells * Megakaryocytes and monocyte subsets may contribute to cytokine storms Summary A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19. Author Affiliation: (1) Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing 100871, China (2) National Center for Liver Cancer, Second Military Medical University, Shanghai 200003, China (3) Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200003, China (4) Ministry of Education (MOE) Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, Shanghai 200003, China (5) Bioland Laboratory (Guangzhou Regenerative Medicine and Health GuangDong Laboratory), Guangzhou 510005, China (6) Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China (7) Beijing Youan Hospital, Capital Medical University, Beijing 100069, China (8) Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230021, China (9) Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, China (10) Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, 150080 Harbin, China (11) State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Brain-Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China (12) State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China (13) Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, China (14) State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China (15) Center for Stem Cell Medicine and Department of Stem Cell & Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China (16) Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China (17) State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China (18) Analytical Biosciences Beijing Limited, Beijing 100084, China (19) State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China (20) Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China (21) State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China (22) Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China (23) Department of Infectious Disease, Shanghai Public Health Clinical Center, Shanghai 201052, China (24) Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing 400038, China (25) Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China (26) Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China (27) Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China (28) Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China (29) Cancer Center, Huanggang Hospital of Traditional Chinese Medicine, Huanggang 438000, China (30) Center for Infection and Immunity, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China (31) Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China (32) Department of Laboratory Medicine, Yuebei People's Hospital, Shantou University Medical College, Shaoguan 512025, China (33) Laboratory for Diagnosis of Clinical Microbiology and Infection, Medical Research Center, Shantou University Medical College, Shaoguan 512025, China (34) Center for Quantitative Biology, Peking University, Beijing 100871, China (35) Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China (36) Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China (37) Yuebei People's Hospital, Shantou University Medical College, Shaoguan 512025, China (38) Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), and Department of Pathology, the First Hospital Affiliated to USTC, Hefei, Anhui 230036, China (39) Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China * Corresponding author Article History: Received 16 September 2020; Revised 9 December 2020; Accepted 28 January 2021 (miscellaneous) Published: February 3, 2021 (footnote)40 These authors contributed equally (footnote)41 Lead contact Byline: Xianwen Ren (1,40), Wen Wen (2,3,4,40), Xiaoying Fan (5,11,40), Wenhong Hou (6,40), Bin Su (7,40), Pengfei Cai (8,40), Jiesheng Li (1,40), Yang Liu (9,40), Fei Tang (1,40), Fan Zhang (10,40), Yu Yang (1,40), Jiangping He (5,40), Wenji Ma (11,40), Jingjing He (12,40), Pingping Wang (13,40), Qiqi Cao (2,3,4), Fangjin Chen (34), Yuqing Chen (1), Xuelian Cheng (14,15), Guohong Deng (16), Xilong Deng (20), Wenyu Ding (11,17), Yingmei Feng (7), Rui Gan (10), Chuang Guo (8), Weiqiang Guo (37), Shuai He (12), Chen Jiang (8), Juanran Liang (19), Yi-min Li (21), Jun Lin (8), Yun Ling (23), Haofei Liu (24), Jianwei Liu (5), Nianping Liu (8), Shu-Qiang Liu (12), Meng Luo (13), Qiang Ma (11), Qibing Song (25), Wujianan Sun (8), GaoXiang Wang (26), Feng Wang (27), Ying Wang (27), Xiaofeng Wen (19), Qian Wu (17), Gang Xu (9), Xiaowei Xie (14,15), Xinxin Xiong (12), Xudong Xing (28), Hao Xu (8), Chonghai Yin (11), Dongdong Yu (25), Kezhuo Yu (1), Jin Yuan (9), Biao Zhang (14,15), Peipei Zhang (24,38,39,40), Tong Zhang (7), Jincun Zhao (21), Peidong Zhao (18), Jianfeng Zhou (26), Wei Zhou (5), Sujuan Zhong (17), Xiaosong Zhong (35), Shuye Zhang (36), Lin Zhu (8), Ping Zhu (14,15), Bin Zou (19), Jiahua Zou (29), Zengtao Zuo (11), Fan Bai (1), Xi Huang (30), Penghui Zhou [zhouph@sysucc.org.cn] (12,*), Qinghua Jiang [qhjiang@hit.edu.cn] (13,**), Zhiwei Huang [huangzhiwei2009@gmail.com] (10,***), Jin-Xin Bei [beijx@sysucc.org.cn] (12,****), Lai Wei [weilai@gzzoc.com] (19,*****), Xiu-Wu Bian [bianxiuwu@263.net] (24,38,******), Xindong Liu [xindongliu@hotmail.com] (24,38,*******), Tao Cheng [chengtao@ihcams.ac.cn] (14,15,********), Xiangpan Li [rm001227@whu.edu.cn] (31,*********), Pingsen Zhao [zhaopingsen01@163.com] (32,33,**********), Fu-Sheng Wang [fswang302@163.com] (28,***********), Hongyang Wang [hywangk@vip.sina.com] (2,3,4,************), Bing Su [bingsu@sjtu.edu.cn] (27,*************), Zheng Zhang [zhangzheng1975@aliyun.com] (9,**************), Kun Qu [qukun@ustc.edu.cn] (8,***************), Xiaoqun Wang [xiaoqunwang@ibp.ac.cn] (5,11,****************), Jiekai Chen [chen_jiekai@gibh.ac.cn] (5,22,*****************), Ronghua Jin [ronghuajin_youan@126.com] (7,******************), Zemin Zhang [zemin@pku.edu.cn] (1,6,41,*******************)

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Gale Document Number: GALE|A657133264