Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.
Haibo Wu, Peiqi He, Yong Ren, Shiqi Xiao, Wei Wang, Zhenbang Liu, Heng Li, Zhe Wang, Dingyu Zhang, Jun Cai, Xiangdong Zhou, Dongpo Jiang, Xiaochun Fei, Lei Zhao, Heng Zhang, Zhenhua Liu, Rong Chen, Weiqing Li, Chaofu Wang, Shuyang Zhang, Jiwei Qin, Björn Nashan, Cheng Sun
Author Information
Haibo Wu: Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Peiqi He: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Yong Ren: Department of Pathology, the First Hospital Affiliated to Army Medical University, Chongqing, 400038, China.
Shiqi Xiao: Department of Pathology, the First Hospital Affiliated to Army Medical University, Chongqing, 400038, China.
Wei Wang: Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Zhenbang Liu: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Heng Li: Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Zhe Wang: Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Jun Cai: Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Xiangdong Zhou: Third Military Medical University Daping Hospital, Chongqing, 400038, China.
Dongpo Jiang: Third Military Medical University Daping Hospital, Chongqing, 400038, China.
Xiaochun Fei: Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Lei Zhao: Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Heng Zhang: Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Zhenhua Liu: Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Rong Chen: Wuhan Jinyintan Hospital, Wuhan, Hubei, 430015, China.
Weiqing Li: Department of Critical Care Medicine, Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, 210002, China.
Chaofu Wang: Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Shuyang Zhang: Peking Union Medical College Hospital, Peking, 100730, China.
Jiwei Qin: Transplant & Immunology Laboratory, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Björn Nashan: Transplant & Immunology Laboratory, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China. ORCID
Cheng Sun: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China. charless@ustc.edu.cn. ORCID
A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1 cells being proximal rather than distal to TIM-3 cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.
