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

Title: Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation
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
Contributors: National Natural Science Foundation of China; Natural Science Foundation of Anhui Province
Source: Nature Communications ; volume 13, issue 1 ; ISSN 2041-1723
Publisher Information: Springer Science and Business Media LLC
Publication Year: 2022
Description: 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.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1038/s41467-021-27723-5
Availability: https://doi.org/10.1038/s41467-021-27723-5; https://www.nature.com/articles/s41467-021-27723-5.pdf; https://www.nature.com/articles/s41467-021-27723-5
Rights: https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0
Accession Number: edsbas.40E5358B
Database: BASE