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

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Updated October 18, 2024

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

Xianwen Ren1
Wen Wen2
Xiaoying Fan3
Wenhong Hou4
Bin Su5
Pengfei Cai6
Jiesheng Li1
Yang Liu7
Fei Tang1
Fan Zhang8
Yu Yang1
Jiangping He9
Wenji Ma10
Jingjing He11
Pingping Wang12
Qiqi Cao2
Fangjin Chen13
Yuqing Chen1
Xuelian Cheng14
Guohong Deng15
Xilong Deng16
Wenyu Ding17
Yingmei Feng5
Rui Gan8
Chuang Guo6
Weiqiang Guo18
Shuai He11
Chen Jiang6
Juanran Liang19
Yi-Min Li20
Jun Lin6
Yun Ling21
Haofei Liu22
Jianwei Liu9
Nianping Liu6
Shu-Qiang Liu11
Meng Luo12
Qiang Ma10
Qibing Song23
Wujianan Sun6
GaoXiang Wang24
Feng Wang25
Ying Wang25
Xiaofeng Wen19
Qian Wu26
Gang Xu7
Xiaowei Xie14
Xinxin Xiong11
Xudong Xing27
Hao Xu6
Chonghai Yin10
Dongdong Yu23
Kezhuo Yu1
Jin Yuan7
Biao Zhang14
Peipei Zhang28
Tong Zhang5
Jincun Zhao20
Peidong Zhao29
Jianfeng Zhou24
Wei Zhou9
Sujuan Zhong26
Xiaosong Zhong30
Shuye Zhang31
Lin Zhu6
Ping Zhu14
Bin Zou19
Jiahua Zou32
Zengtao Zuo10
Fan Bai1
Xi Huang33
Penghui Zhou34
Qinghua Jiang35
Zhiwei Huang36
Jin-Xin Bei37
Lai Wei38
Xiu-Wu Bian39
Xindong Liu40
Tao Cheng41
Xiangpan Li42
Pingsen Zhao43
Fu-Sheng Wang44
Hongyang Wang45
Bing Su46
Zheng Zhang47
Kun Qu48
Xiaoqun Wang49
Jiekai Chen50
Ronghua Jin51
Zemin Zhang52
1Biomedical 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.
2National 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.
3Bioland 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.
4Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China.
5Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
6Department 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.
7Institute 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.
8Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, 150080 Harbin, China.
9Bioland Laboratory (Guangzhou Regenerative Medicine and Health GuangDong Laboratory), Guangzhou 510005, China.
10State 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.
11State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
12Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, China.
13Center for Quantitative Biology, Peking University, Beijing 100871, China.
14State 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.
15Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China.
16Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
17State 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; State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
18Yuebei People's Hospital, Shantou University Medical College, Shaoguan 512025, China.
19State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
20State 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.
21Department of Infectious Disease, Shanghai Public Health Clinical Center, Shanghai 201052, China.
22Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing 400038, China.
23Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
24Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
25Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
26State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
27Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China.
28Institute 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; Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
29Analytical Biosciences Beijing Limited, Beijing 100084, China.
30Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
31Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China.
32Cancer Center, Huanggang Hospital of Traditional Chinese Medicine, Huanggang 438000, China.
33Center for Infection and Immunity, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
34State 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.
35Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, China. Electronic address: qhjiang@hit.edu.cn.
36Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, 150080 Harbin, China. Electronic address: huangzhiwei2009@gmail.com.
37State 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.
38State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. Electronic address: weilai@gzzoc.com.
39Institute 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.
40Institute 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.
41State 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.
42Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: rm001227@whu.edu.cn.
43Department 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.
44Department 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.
45National 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.
46Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: bingsu@sjtu.edu.cn.
47Institute 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.
48Department 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.
49Bioland 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.
50Bioland 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.
51Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. Electronic address: ronghuajin_youan@126.com.
52Biomedical 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.
Wei Kheng Teh

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/5f607e50-ba22-4598-b1e9-f3d9d7a35dcc

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.http://covid19.cancer-pku.cn
GEO Series Accessions:

Atlas

LungLung v2.0

Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

CovidImmuneAtlas

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

2 anatomical entities

Organ Part

Unspecified

Selected Cell Types

6 cell types

Disease Status (Specimen)

3 disease statuses

Disease Status (Donor)

45 disease statuses

Development Stage

human adult stage

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

processed_matrix, raw_matrix

File Format

5 file formats

Cell Count Estimate

1.5M

Donor Count

196
csv1 file(s)h5ad.tar.gz1 file(s)mtx.gz1 file(s)tsv4 file(s)xlsx1 file(s)