Transcriptomic analysis of COVID‑19 lungs and bronchoalveolar lavage fluid samples reveals predominant B cell activation responses to infection

Abstract

The outbreak of the 2019 coronavirus disease (named, COVID‑19), caused by the novel SARS‑CoV‑2 virus, represents a worldwide severe threat to public health. It is of the utmost importance to characterize the immune responses against the SARS‑CoV‑2 and the mechanisms of hyperinflammation, in order to design better therapeutic strategies for COVID‑19. In the present study, a transcriptomic analysis was performed to profile the immune signatures in lung and the bronchoalveolar lavage fluid samples from COVID‑19 patients and controls. Our data concordantly revealed increased humoral responses to infection. The elucidation of the host responses to SARS‑CoV‑2 infection may further improve our understanding of COVID‑19 pathogenesis and suggest better therapeutic strategies.

Figure 1

Enrichment and network analysis of COVID-19 lung samples. (A) Hierarchical clustering of the top most enriched terms among the genes signifi-cantly upregulated and downregulated in the GSE150316 dataset. The heatmap is colored based on the p-values, and grey cells indicate the lack of significant enrichment. (B) Gene expression heatmap of the genes belonging to the GO:0002377 (immunoglobulin production) category, in lung biopsies of COVID-19 patients and control samples, as determined in the GSE150316 dataset.

Figure 2

Enrichment and network analysis of COVID-19 samples. (A) Scatter plot showing the correlation of the gene expression profile between the GSE150316 and the GSE147507 datasets. (B) Hierarchical clustering of the top most enriched terms among the genes significantly upregulated and downregu-lated in the GSE150316 and the GSE147507 datasets. The heatmap is colored based on the p-values, and grey cells indicate the lack of significant enrichment. (C) Representative terms from the enrichment analysis are presented as a network, visualized as a 'force-directed' layout. Description of each term is shown as a label.

Figure 3

Deconvolution analysis of infiltrating immune cells in lung samples from COVID-19 patients and controls as determined in the GSE150316. (A) Histogram plot for the ImuneScore, StromaScore an MicroenviromentScore in lung samples from COVID-19 patients and controls, as determined in the GSE150316. (B) Relative proportions of infiltrating myeloid cells in lung samples from COVID-19 patients and controls, as determined in the GSE150316. (C) Relative proportions of infiltrating lymphoid cells in lung samples from COVID-19 patients and controls, as determined in the GSE150316.

Figure 4

Characterization of the transcriptomic profile of BALF samples from COVID-19 patients and controls. (A) Hierarchical clustering of the top most enriched terms by genes significantly upregulated and downregulated in the BALF samples of COVID-19 patients as compared to control samples. (B) Hierarchical clustering of the top predicted transcription factors involved in the expression of the genes significantly upregulated and downregulated in the BALF samples of COVID-19 patients as compared to control samples. (C) Deconvolution analysis of infiltrating immune cells in BALF samples from COVID-19 patients and controls.