COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a 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 are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation 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 of and developing effective therapeutic strategies for COVID-19. [Display omitted] •Detailed COVID-19 immune landscape depicted by integrated 1.46 million single cells•Peripheral immune subtypes differentially associated with distinct clinical features•SARS-CoV-2 RNA is present in diverse epithelial and immune cells•Megakaryocytes and monocyte subsets may contribute to cytokine storms Analysis of the immune landscape in the lung and peripheral blood of COVID patients across different regions in China at the single-cell level documents the presence of viral RNAs in diverse cell types and highlights the potential contribution of megakaryocytes and monocyte subsets to cytokine storms.