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. 2024 Sep 27;14(1):22044.
doi: 10.1038/s41598-024-69635-6.

RNA-Seq analysis of human heart tissue reveals SARS-CoV-2 infection and inappropriate activation of the TNF-NF-κB pathway in cardiomyocytes

Kirtan Dave  1   2 , Mukul Jain  3   4 , Meenakshi Sharma  5 , Anil Kumar Delta  5 , Chittaranjan Kole  6 , Prashant Kaushik  7
Affiliations

RNA-Seq analysis of human heart tissue reveals SARS-CoV-2 infection and inappropriate activation of the TNF-NF-κB pathway in cardiomyocytes

Kirtan Dave et al. Sci Rep. .

Abstract

The negative impact of SARS-CoV-2 virus infection on cardiovascular disease (CVD) patients is well established. This research article explores the cellular pathways involved in underlying heart diseases after infection. The systemic inflammatory response to SARS-CoV-2 infection likely exacerbates this increased cardiovascular risk; however, whether the virus directly infects cardiomyocytes remains unknown due to limited multi-omics data. While public transcriptome data exists for COVID-19 infection in different cell types (including cardiomyocytes), infection times vary between studies. We used available RNA-seq data from human heart tissue to delineate SARS-CoV-2 infection and heart failure aetiology specific gene expression signatures. A total of fifty-four samples from four studies were analysed. Our aim was to investigate specific transcriptome changes occurring in cardiac tissue with SARS-CoV-2 infection compared to non-infected controls. Our data establish that SARS-CoV-2 infects cardiomyocytes by the TNF-NF-κB pathway, potentially triggering acute cardiovascular complications and increasing the long-term cardiovascular risk in COVID-19 patients.

Keywords: Bioinformatics; COVID-19; Cardiomyocytes; Gene; Heart failure; RNA-seq; TNF-NF-κB.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Putative signaling pathway of SARS-COV-2 interaction with heart tissue causing heart damage and heart failure.
Figure 2
Figure 2
Volcano plots of the differential gene expression data from GSE150392, GSE151879, and GSE156754. In the volcano plots, the red points show up-regulated genes (log2FC ≥ 0.5 and adjusted P-value < 0.05). The Venn map of the differentially expressed genes, however, shows the up-regulated genes as red dots. The number within each circle denotes the quantity of genes that exhibit differential expression across the various comparisons. We took into account only the designated genes. The genes specific to each condition are indicated by the non-overlapping numbers, whereas the overlapping number represents the genes that are mutually differentially expressed between the various comparisons.
Figure 3
Figure 3
Heat map of the top differentially expressed genes based on GSE150392, GSE151879, and GSE156754. The colour intensity suggests the higher to lower expression pathway and pathway enrichment analysis.
Figure 4
Figure 4
GO analyses of genes that are elevated and downregulated and analysis of the GO function enrichment (including BP, MF, and CC). B. Analysis of KEGG pathway enrichment. The gene ratio is displayed on the x-axis, while the GO category is displayed on the y-axis. The size of the bar represents the number of genes included in the relevant pathway, and the significance of enrichment progressively grows from blue to red.
Figure 5
Figure 5
Differentially expression of TNF-NF-κB pathway genes from DEG analysis.
See this image and copyright information in PMC

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