Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world. The development of cardiac injury is a common condition in patients with COVID-19, but the pathogenesis remains unclear. The RNA-Seq dataset (GSE150392) comparing expression profiling of mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was obtained from Gene Expression Omnibus (GEO). We identified 1,554 differentially expressed genes (DEGs) based on GSE150392. Gene set enrichment analysis (GSEA), Gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that immune-inflammatory responses were activated by SARS-CoV-2, while muscle contraction, cellular respiration, and cell cycle of hiPSC-CMs were inhibited. A total of 15 hub genes were identified according to protein–protein interaction (PPI), among which 11 upregulated genes were mainly involved in cytokine activation related to the excessive inflammatory response. Moreover, we identified potential drugs based on these hub genes. In conclusion, SARS-CoV-2 infection of cardiomyocytes caused a strong defensive response, leading to excessive immune inflammation, cell hypoxia, functional contractility reduction, and apoptosis, ultimately resulting in myocardial injury.
Highlights
Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]
Gene set enrichment analysis demonstrated that many inflammation-related gene sets, such as TNFα signaling via NF-κB, interferon-γ response, interferonα response, inflammatory response, IL6-JAK-STAT3 signaling, IL2-STAT5 signaling, hypoxia, P53 pathway, and apoptosis gene sets were enriched by SARS-CoV-2 infection in hiPSCCMs
E2F targets, G2M checkpoint, myogenesis, and MYC targets v1 gene sets associated with cell cycle, aerobic respiration, and myogenesis were inhibited in hiPSC-CMs with SARS-CoV-2 infection
Summary
Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. In December 2019, COVID-19 was first reported in Wuhan of China as a severe unknown form of pneumonia. At the time of preparing this manuscript, there were more than 5,00,000 fatalities caused by COVID-19. Acute myocardial damage is the most common described cardiovascular (CV) complication in patients with COVID-19 [2]. Cytokine storms (caused by acute systemic inflammation) [1, 4], hypoxemia [5], and pathogen-mediated damage [6, 7] were considered as the potential mechanisms responsible for CV complications in COVID-19. The exact mechanism of SARS-CoV-2 infection-related myocardial injury remains unclear
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