1. Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.
- Author
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Wu H, He P, Ren Y, Xiao S, Wang W, Liu Z, Li H, Wang Z, Zhang D, Cai J, Zhou X, Jiang D, Fei X, Zhao L, Zhang H, Liu Z, Chen R, Li W, Wang C, Zhang S, Qin J, Nashan B, and Sun C
- Subjects
- Aged, Autopsy, COVID-19 diagnosis, COVID-19 genetics, COVID-19 virology, China, Diagnosis, Female, Hepatitis A Virus Cellular Receptor 2 genetics, Hepatitis A Virus Cellular Receptor 2 immunology, Humans, Immunosuppression Therapy, Lymphocyte Activation, Lymphocytes immunology, Male, Middle Aged, Myeloid Cells immunology, Programmed Cell Death 1 Receptor genetics, Programmed Cell Death 1 Receptor immunology, SARS-CoV-2 immunology, Viral Load, COVID-19 immunology, SARS-CoV-2 physiology
- 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., (© 2022. The Author(s).)- Published
- 2022
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