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. 2022 Jul 15:13:918383.
doi: 10.3389/fimmu.2022.918383. eCollection 2022.

A Landscape Study on COVID-19 Immunity at the Single-Cell Level

Rongguo Wei  1   2   3 , Zheng Qin  3   4 , Qi Huang  3   4 , Lulu Liu  1   2 , Fang Cheng  1   2 , Songdong Meng  1   2 , Lin Wang  3   4
Affiliations

A Landscape Study on COVID-19 Immunity at the Single-Cell Level

Rongguo Wei et al. Front Immunol. .

Abstract

Since 2019, the coronavirus (COVID-19) has outbroken continuously, spreading internationally and threatening the public health. However, it was unknown how the disorder at the single-cell level was associated with the pathogenesis of COVID-19. This study presented the disorders of macrophages, epithelial cells, CD8+ T cells, and natural killer (NK) cells at the single-cell level in the courses of COVID-19 and analyzed the immune response to cytokine storm. Compared with the healthy group, patients with COVID-19 had higher proportions of macrophages and lower proportions of T and NK cells, especially proportions of macrophages and epithelial cells with an increase during patients' conditions from mild to severe. This study suggested that there were high levels of pro-inflammatory and chemokine expressions in cells of COVID-19 and analyzed cell subsets to explore its changes and pathways. It was worth noting that several subsets of macrophages, epithelial cells, CD8 T cells, and NK cells were involved in inflammation pathways, including interleukin-17 (IL-17) signaling pathway and tumor necrosis factor (TNF) signaling pathway. Moreover, the pathways interacting COVID-19 and cytokine receptor with each other were remarkably enriched. In addition, these cell subsets played important roles in inflammation, and their abnormal functions may cause COVID-19. In conclusion, this study provided an immune outlook for COVID-19 at the single-cell level and revealed different pathways in immune response of COVID-19 single cells.

Keywords: COVID-19; cytokines; immunity; signaling pathway; single-cell.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Global single-cell spectrum of COVID-19. (A) Global single-cell spectrum of COVID-19, with a total of 1,529,428 cells and 239 clusters obtained. (B) A total of 239 clusters were divided into different cell types based on known marker genes. (C, D) clusters of cells with marker genes mapped in the single-cell spectrum of CD8 T cells (CD8A and CD8B), macrophages (CD68), NK cells (NCAM1), EP cells (EPCAM1 and CEACAM1), and B cells (MS4A1 and CD19). (E) Cytobiological components and changes in the healthy and COVID-19 groups. (F) Cytobiological components and changes in the healthy group and patients with COVID-19 with different courses (asymptomatic, mild, and severe). EP cell, epithelial cell; KEGG, Kyoto Encyclopedia of Genes and Genomes; NK cell, natural killer cell; UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction.
Figure 2
Figure 2
Abnormal components of macrophage in patients with COVID-19. (A) Single-cell mapping of subsets of macrophages. (B) Single-cell mapping of macrophages mapped in the COVID-19 courses. (C) Components and changes of macrophage subsets in the COVID-19 courses. (D, E) Expression of marker genes in macrophage subsets. (F) Biological pathways involved in macrophage subsets with specific changes. KEGG, Kyoto Encyclopedia of Genes and Genomes; Mac, macrophage; UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction.
Figure 3
Figure 3
Abnormal components of epithelial cell in patients with COVID-19. (A) Single-cell mapping of EP cell subsets. (B) Single-cell mapping of EP cells in the COVID-19 courses. (C) Components and changes of epithelial cell subsets in the courses of new crowns. (D, E) Expression of marker genes in subsets of EP cells. (F) Biological pathways involved in subsets of EP cells with specific changes. EP, epithelial cell; KEGG, Kyoto Encyclopedia of Genes and Genomes; UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction.
Figure 4
Figure 4
Abnormal components of CD8 T cell in patients with COVID-19. (A) Single-cell mapping of CD8 T cell subsets. (B) Single-cell mapping of CD8 T cells in the COVID-19 courses. (C) Components and changes in CD8 T cell subsets in the COVID-19 courses. (D, E) Expression of marker genes in CD8 T cell subsets. (F) CD8 T cells with specific changes in subsets involved in biological pathways. KEGG, Kyoto Encyclopedia of Genes and Genomes; UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction.
Figure 5
Figure 5
Abnormal components of NK cell in patients with COVID-19. (A) Single-cell mapping of NK cell subsets. (B) Single-cell mapping of NK cells in the COVID-19 courses. (C) Components and changes of subpopulations of NK cells in the courses of new crowns. (D, E) Expression of marker genes in NK cell subsets. (F) Biological pathways involved in NK cell subsets with specific changes. KEGG, Kyoto Encyclopedia of Genes and Genomes; NK, natural killer cell; UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction.
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