Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation

• Published in: Nature communications 2022-01, Vol.13 (1), p.269-269, Article 269
• Main Authors: Wu, Haibo, He, Peiqi, Ren, Yong, Xiao, Shiqi, Wang, Wei, Liu, Zhenbang, Li, Heng, Wang, Zhe, Zhang, Dingyu, Cai, Jun, Zhou, Xiangdong, Jiang, Dongpo, Fei, Xiaochun, Zhao, Lei, Zhang, Heng, Liu, Zhenhua, Chen, Rong, Li, Weiqing, Wang, Chaofu, Zhang, Shuyang, Qin, Jiwei, Nashan, Björn, Sun, Cheng
• Format: Article
• Language: English
• Subjects: 38/1; 38/39; 49/91; 631/250/2502; 631/250/2503; 631/250/255/2514; 631/553/1833; Aged; Antigens; Autopsies; Autopsy; China; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - virology; Dendritic cells; Diagnosis; Etiology; Female; Hepatitis A Virus Cellular Receptor 2 - genetics; Hepatitis A Virus Cellular Receptor 2 - immunology; Humanities and Social Sciences; Humans; Immunosuppression; Immunosuppression Therapy; Infections; Lymphocyte Activation; Lymphocytes; Lymphocytes - immunology; Male; Middle Aged; multidisciplinary; Myeloid cells; Myeloid Cells - immunology; Organs; Pathogenesis; PD-1 protein; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - immunology; SARS-CoV-2 - immunology; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Transcription; Transcriptomics; Viral diseases; Viral infections; Viral Load
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27723-5

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. Postmortem analyses provide useful information for COVID-19 etiology. Here the authors profile 22 deceased severe COVID-19 patients with transcriptomic and histological approaches to find correlations between the presence of viral antigens with lymphocyte suppression yet myeloid activation, hinting distinct functions of these cells during pathogenesis.