COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas
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...
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| Published in: | Cell Vol. 184; no. 7; p. 1895 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
01.04.2021
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| Subjects: | |
| ISSN: | 1097-4172, 1097-4172 |
| Online Access: | Get more information |
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| Abstract | 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. |
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| AbstractList | 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.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. 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 | Wen, Wen Liu, Xindong Wang, Ying Xie, Xiaowei Liang, Juanran Ding, Wenyu Chen, Jiekai Li, Jiesheng Zhang, Biao He, Shuai Yuan, Jin Zou, Bin Jiang, Qinghua Zhang, Zheng He, Jingjing Qu, Kun Zhou, Jianfeng Zhao, Pingsen Xu, Gang Wei, Lai Wang, Fu-Sheng Zhu, Lin Song, Qibing Zhong, Xiaosong Xing, Xudong Chen, Yuqing Bai, Fan Fan, Xiaoying Liu, Yang Hou, Wenhong Zhang, Fan Li, Yi-Min Ling, Yun Zhong, Sujuan Guo, Chuang Zuo, Zengtao Wang, Pingping Cao, Qiqi Jiang, Chen Deng, Xilong Zou, Jiahua He, Jiangping Deng, Guohong Luo, Meng Ma, Qiang Tang, Fei Xu, Hao Sun, Wujianan Zhao, Jincun Cai, Pengfei Wang, GaoXiang Huang, Xi Zhang, Shuye Bian, Xiu-Wu Ma, Wenji Zhang, Peipei Wang, Xiaoqun Zhang, Tong Wen, Xiaofeng Gan, Rui Jin, Ronghua Liu, Shu-Qiang Huang, Zhiwei Xiong, Xinxin Yin, Chonghai Su, Bing Zhang, Zemin Cheng, Xuelian Feng, Yingmei Lin, Jun Ren, Xianwen Bei, Jin-Xin Wu, Qian Yang, Yu Liu, Jianwei Guo, Weiqiang Zhou, Wei Zhu, Ping Liu, Haofei Liu, Nianping Zhao, Peidong Zhou, Penghui Wang, Feng Yu, Dongdong Wang, Hongyang Su, Bin Li, Xiangpan Chen, Fangjin Cheng, Tao Yu, K |
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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 – sequence: 4 givenname: Wenhong surname: Hou fullname: Hou, Wenhong organization: Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China – sequence: 5 givenname: Bin surname: Su fullname: Su, Bin organization: Beijing Youan Hospital, Capital Medical University, Beijing 100069, China – sequence: 6 givenname: Pengfei surname: Cai fullname: Cai, Pengfei organization: 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 – sequence: 7 givenname: Jiesheng surname: Li fullname: Li, Jiesheng organization: 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givenname: Jingjing surname: He fullname: He, Jingjing organization: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China – sequence: 15 givenname: Pingping surname: Wang fullname: Wang, Pingping organization: Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, China – sequence: 16 givenname: Qiqi surname: Cao fullname: Cao, Qiqi organization: National Center for Liver Cancer, Second Military Medical University, Shanghai 200003, China; Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200003, China; Ministry of Education (MOE) Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, Shanghai 200003, China – sequence: 17 givenname: Fangjin surname: Chen fullname: Chen, Fangjin organization: Center for Quantitative Biology, Peking University, 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China, Hefei, Anhui 230021, China – sequence: 51 givenname: Chonghai surname: Yin fullname: Yin, Chonghai organization: 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 – sequence: 52 givenname: Dongdong surname: Yu fullname: Yu, Dongdong organization: Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China – sequence: 53 givenname: Kezhuo surname: Yu fullname: Yu, Kezhuo organization: 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 – sequence: 54 givenname: Jin surname: Yuan fullname: Yuan, Jin organization: Institute for Hepatology, National Clinical 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Science and Technology of China (USTC), and Department of Pathology, the First Hospital Affiliated to USTC, Hefei, Anhui 230036, China; Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China – sequence: 57 givenname: Tong surname: Zhang fullname: Zhang, Tong organization: Beijing Youan Hospital, Capital Medical University, Beijing 100069, China – sequence: 58 givenname: Jincun surname: Zhao fullname: Zhao, Jincun organization: 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 – sequence: 59 givenname: Peidong surname: Zhao fullname: Zhao, Peidong organization: Analytical Biosciences Beijing Limited, Beijing 100084, China – sequence: 60 givenname: Jianfeng surname: Zhou fullname: Zhou, Jianfeng organization: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China – sequence: 61 givenname: Wei surname: Zhou fullname: Zhou, Wei organization: Bioland Laboratory (Guangzhou Regenerative Medicine and Health GuangDong Laboratory), Guangzhou 510005, China – sequence: 62 givenname: Sujuan surname: Zhong fullname: Zhong, Sujuan organization: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China – sequence: 63 givenname: Xiaosong surname: Zhong fullname: Zhong, Xiaosong organization: Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China – sequence: 64 givenname: Shuye surname: Zhang fullname: Zhang, Shuye organization: Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China – sequence: 65 givenname: Lin surname: Zhu fullname: Zhu, Lin organization: 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 – sequence: 66 givenname: Ping surname: Zhu fullname: Zhu, Ping organization: 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; 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 – sequence: 67 givenname: Bin surname: Zou fullname: Zou, Bin organization: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China – sequence: 68 givenname: Jiahua surname: Zou fullname: Zou, Jiahua organization: Cancer Center, Huanggang Hospital of Traditional Chinese Medicine, Huanggang 438000, China – sequence: 69 givenname: Zengtao surname: Zuo fullname: Zuo, Zengtao organization: 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 – sequence: 70 givenname: Fan surname: Bai fullname: Bai, Fan organization: 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 – sequence: 71 givenname: Xi surname: Huang fullname: Huang, Xi organization: Center for Infection and Immunity, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China – sequence: 72 givenname: Penghui surname: Zhou fullname: Zhou, Penghui email: zhouph@sysucc.org.cn organization: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: zhouph@sysucc.org.cn – sequence: 73 givenname: Qinghua surname: Jiang fullname: Jiang, Qinghua email: qhjiang@hit.edu.cn organization: Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, China. Electronic address: qhjiang@hit.edu.cn – sequence: 74 givenname: Zhiwei surname: Huang fullname: Huang, Zhiwei email: huangzhiwei2009@gmail.com organization: Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, 150080 Harbin, China. Electronic address: huangzhiwei2009@gmail.com – sequence: 75 givenname: Jin-Xin surname: Bei fullname: Bei, Jin-Xin email: beijx@sysucc.org.cn organization: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: beijx@sysucc.org.cn – sequence: 76 givenname: Lai surname: Wei fullname: Wei, Lai email: weilai@gzzoc.com organization: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. Electronic address: weilai@gzzoc.com – sequence: 77 givenname: Xiu-Wu surname: Bian fullname: Bian, Xiu-Wu email: bianxiuwu@263.net organization: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing 400038, China; 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. Electronic address: bianxiuwu@263.net – sequence: 78 givenname: Xindong surname: Liu fullname: Liu, Xindong email: xindongliu@hotmail.com organization: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing 400038, China; 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. Electronic address: xindongliu@hotmail.com – sequence: 79 givenname: Tao surname: Cheng fullname: Cheng, Tao email: chengtao@ihcams.ac.cn organization: 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; 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. Electronic address: chengtao@ihcams.ac.cn – sequence: 80 givenname: Xiangpan surname: Li fullname: Li, Xiangpan email: rm001227@whu.edu.cn organization: Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: rm001227@whu.edu.cn – sequence: 81 givenname: Pingsen surname: Zhao fullname: Zhao, Pingsen email: zhaopingsen01@163.com organization: Department of Laboratory Medicine, Yuebei People's Hospital, Shantou University Medical College, Shaoguan 512025, China; Laboratory for Diagnosis of Clinical Microbiology and Infection, Medical Research Center, Shantou University Medical College, Shaoguan 512025, China. Electronic address: zhaopingsen01@163.com – sequence: 82 givenname: Fu-Sheng surname: Wang fullname: Wang, Fu-Sheng email: fswang302@163.com organization: Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China. Electronic address: fswang302@163.com – sequence: 83 givenname: Hongyang surname: Wang fullname: Wang, Hongyang email: hywangk@vip.sina.com organization: National Center for Liver Cancer, Second Military Medical University, Shanghai 200003, China; Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200003, China; Ministry of Education (MOE) Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, Shanghai 200003, China. Electronic address: hywangk@vip.sina.com – sequence: 84 givenname: Bing surname: Su fullname: Su, Bing email: bingsu@sjtu.edu.cn organization: Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: bingsu@sjtu.edu.cn – sequence: 85 givenname: Zheng surname: Zhang fullname: Zhang, Zheng email: zhangzheng1975@aliyun.com organization: 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. Electronic address: zhangzheng1975@aliyun.com – sequence: 86 givenname: Kun surname: Qu fullname: Qu, Kun email: qukun@ustc.edu.cn organization: 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. Electronic address: qukun@ustc.edu.cn – sequence: 87 givenname: Xiaoqun surname: Wang fullname: Wang, Xiaoqun email: xiaoqunwang@ibp.ac.cn organization: Bioland Laboratory (Guangzhou Regenerative Medicine and Health GuangDong Laboratory), Guangzhou 510005, China; 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. Electronic address: xiaoqunwang@ibp.ac.cn – sequence: 88 givenname: Jiekai surname: Chen fullname: Chen, Jiekai email: chen_jiekai@gibh.ac.cn organization: Bioland Laboratory (Guangzhou Regenerative Medicine and Health GuangDong Laboratory), Guangzhou 510005, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: chen_jiekai@gibh.ac.cn – sequence: 89 givenname: Ronghua surname: Jin fullname: Jin, Ronghua email: ronghuajin_youan@126.com organization: Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. Electronic address: ronghuajin_youan@126.com – sequence: 90 givenname: Zemin surname: Zhang fullname: Zhang, Zemin email: zemin@pku.edu.cn organization: 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; Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: zemin@pku.edu.cn |
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| Keywords | COVID-19 SARS-CoV-2 single-cell transcriptomics cytokine storm host cell range B cell receptor sequencing cell-cell interaction single-cell RNA-seq ligand-receptor interaction T cell receptor sequencing |
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| References | 34767776 - Cell. 2021 Nov 11;184(23):5838 33863870 - Signal Transduct Target Ther. 2021 Apr 16;6(1):156 |
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| Title | COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas |
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