tetano
Editor, Senior Moderator
Nat Commun
. 2022 Jan 12;13(1):269.
doi: 10.1038/s41467-021-27723-5.
Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation
Haibo Wu[SUP] #[/SUP][SUP] 1 [/SUP], Peiqi He[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Yong Ren[SUP] #[/SUP][SUP] 5 [/SUP], Shiqi Xiao[SUP] 5 [/SUP], Wei Wang[SUP] 1 [/SUP], Zhenbang Liu[SUP] 2 [/SUP], Heng Li[SUP] 1 [/SUP], Zhe Wang[SUP] 1 [/SUP], Dingyu Zhang[SUP] 6 [/SUP], Jun Cai[SUP] 7 [/SUP], Xiangdong Zhou[SUP] 8 [/SUP], Dongpo Jiang[SUP] 8 [/SUP], Xiaochun Fei[SUP] 7 [/SUP], Lei Zhao[SUP] 7 [/SUP], Heng Zhang[SUP] 7 [/SUP], Zhenhua Liu[SUP] 7 [/SUP], Rong Chen[SUP] 6 [/SUP], Weiqing Li[SUP] 9 [/SUP], Chaofu Wang[SUP] 7 [/SUP], Shuyang Zhang[SUP] 10 [/SUP], Jiwei Qin[SUP] 4 [/SUP], Björn Nashan[SUP] 4 [/SUP], Cheng Sun[SUP] 11 12 13 [/SUP]
Affiliations
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[SUP]+[/SUP] cells being proximal rather than distal to TIM-3[SUP]+[/SUP] 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.
. 2022 Jan 12;13(1):269.
doi: 10.1038/s41467-021-27723-5.
Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation
Haibo Wu[SUP] #[/SUP][SUP] 1 [/SUP], Peiqi He[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Yong Ren[SUP] #[/SUP][SUP] 5 [/SUP], Shiqi Xiao[SUP] 5 [/SUP], Wei Wang[SUP] 1 [/SUP], Zhenbang Liu[SUP] 2 [/SUP], Heng Li[SUP] 1 [/SUP], Zhe Wang[SUP] 1 [/SUP], Dingyu Zhang[SUP] 6 [/SUP], Jun Cai[SUP] 7 [/SUP], Xiangdong Zhou[SUP] 8 [/SUP], Dongpo Jiang[SUP] 8 [/SUP], Xiaochun Fei[SUP] 7 [/SUP], Lei Zhao[SUP] 7 [/SUP], Heng Zhang[SUP] 7 [/SUP], Zhenhua Liu[SUP] 7 [/SUP], Rong Chen[SUP] 6 [/SUP], Weiqing Li[SUP] 9 [/SUP], Chaofu Wang[SUP] 7 [/SUP], Shuyang Zhang[SUP] 10 [/SUP], Jiwei Qin[SUP] 4 [/SUP], Björn Nashan[SUP] 4 [/SUP], Cheng Sun[SUP] 11 12 13 [/SUP]
Affiliations
- PMID: 35022412
- DOI: 10.1038/s41467-021-27723-5
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[SUP]+[/SUP] cells being proximal rather than distal to TIM-3[SUP]+[/SUP] 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.