Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes were associated with distinct clinical features including age, sex, severity, and disease stages of COVID-19. SARS-CoV-2 RNAs were found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within viral positive cells. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and developing effective therapeutic strategies for COVID-19.

No abstract

Highlights d Integrative analysis of single-cell transcriptomes from three infectious diseases d Hyperinflammatory signatures of monocytes differ in these infections d A ''three-stage'' model of COVID-19 patients is related to inflammatory signatures

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an “immunosuppressive” microenvironment are poorly understood.

Human cystic echinococcosis, caused by the larval stage of echinococcus granulus sensu lato , has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce lesion microenvironment, however cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironment are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, peri-lesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations, and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between peri-lesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of innate lymphocyte 2 and plasmacytoid dendritic cells were higher in peri-lesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was up-regulated in these cells. Seven subsets of CD4 + T cell populations were found, and there were more Treg-CD4 + T and Th2-CD4 + T cells in peri-lesion tissue than those in adjacent normal tissue. There was close contact between CD4 + T cells and ILC2 and pDCs cells, which caused up-regulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in peri-lesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the CE lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironment at single-cell level, and provides potential target signatures for diagnosis and immunotherapies.