Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Abstract

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 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. 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 designing effective therapeutic strategies for COVID-19.

Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV-2 infection

“…A number of high-resolution studies have recently concentrated on the determination of circulating markers that can distinguish severe from mild forms of COVID-19, providing a tremendous amount of data describing phenotypic and functional alterations in T cell, B cell, and myeloid cell subsets. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] In particular, CD14 + HLA-DR low , CD14 + CD16 + , and immature monocytes were demonstrated to be increased among peripheral blood mononuclear cells (PBMCs) from critically ill COVID-19 patients. 15,21,23,[26][27][28][29] Interestingly, the monocyte number is reduced in COVID-19 patients compared to influenza patients, suggesting specific myeloid dysregulation.…”

A comprehensive review of the analysis and integration of omics data for SARS-CoV-2 and COVID-19

“…Recently, an article titled ‘Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients’ applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients to generate a large dataset including ~1.5 million single cells and controls. It created a comprehensive immune landscape, providing abundant resources for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19 patients [ 58 ]. We also manually collated the single-cell RNA-sequencing datasets ( Supplementary Table 1 available online at http://bib.oxfordjournals.org/ ) and bulk RNA-sequencing datasets ( Supplementary Table 2 available online at http://bib.oxfordjournals.org/ ) containing the raw data from the GEO database, including lung, kidney, brain, intestine and other tissues/organs.…”