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.
【저자키워드】 viral infection, Systems analysis, Imaging the immune system, Gene regulation in immune cells, 【초록키워드】 COVID-19, coronavirus disease, viral infection, Coronavirus disease 2019, immune response, therapy, Pathogenesis, Lymphocytes, severe COVID-19, SARS-COV-2 infection, myeloid cells, diagnostic, Immunosuppression, progression, Autopsy, COVID-19 disease, PD-1, lymphocyte, Viral, Viral load, cells, immune responses, immune profiling, Wuhan, antigens, Postmortem, etiology, correlation, information, dendritic cell, severe COVID-19 disease, function, Analysis, Deceased, cell types, cell type, Viral antigen, Activation, viral antigens, These cells, correlations, multiple organs, hallmark, myeloid cell, SARS-CoV-2 viral infection, Complete, men, transcriptomic, approach, Cell, prevalent, transcriptional, Wuhan, China, SARS-CoV-2 viral, activated, induce, these cell, proximal, histological, distal, severe COVID-19 patient, 【제목키워드】 Immunosuppression, immune profiling, Postmortem, reveal, severe COVID-19 patient,