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

• DOI: 10.1038/s41467-021-27723-5
• Publication Date: 2022-01-12T11:02:59Z
• Authors: Haibo Wu; Peiqi He; Yong Ren; Shiqi Xiao; Wei Wang; Zhenbang Liu; Heng Li; Zhe Wang; Dingyu Zhang; Jun Cai; Xiangdong Zhou; Dongpo Jiang; Xiaochun Fei; Lei Zhao; Heng Zhang; Zhenhua Liu; Rong Chen; Weiqing Li; Chaofu Wang; Shuyang Zhang; Jiwei Qin; Björn Nashan; Cheng Sun
• Keywords: Immunosuppression Therapy; Male; 0301 basic medicine; China; SARS-CoV-2; Science; Q; Programmed Cell Death 1 Receptor; COVID-19; Middle Aged; Viral Load; Lymphocyte Activation; Article; 3. Good health; 03 medical and health sciences; Diagnosis; Humans; Female; Myeloid Cells; Autopsy; Lymphocytes; Hepatitis A Virus Cellular Receptor 2; Aged

AbstractA 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.