1. Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.
- Author
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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, and Zhang, Shuyang
- Subjects
COVID-19 ,VIRUS diseases ,AUTOPSY ,VIRAL antigens ,MYELOID cells ,IMMUNOSUPPRESSION ,SARS-CoV-2 - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2022
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