Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma

Abstract

BackgroundThe coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma.MethodsTwo sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury.ResultsWe discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein–protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor–gene interactions, DEG–microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes.ConclusionWe identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.

A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection

“…KEGG pathway analysis revealed several shared pathways between sepsis and COVID-19, including asthma, inflammatory bowel disease (IBD), hematopoietic cell lineage, intestinal immune network for IgA production, legionellosis, staphylococcus aureus infection, leishmaniasis, Th1 and Th2 cell differentiation, systemic lupus erythematosus, and cytokine-cytokine receptor interactions. We and others have shown a strong relationship between COVID-19 and asthma, and further connections have been established between COVID-19, asthma, and legionellosis ( 35 , 36 ). IBD, COVID-19, and sepsis share a link to the gut microbiota, which is a critical factor in regulating the host’s susceptibility to SARS-CoV-2 infection and clearance ( 37 , 38 ).…”

“…At the molecular level, we observed significant connections between COVID-19 and sepsis, particularly in the context of TFs and miRNAs. Both TFs and miRNAs play crucial roles in regulating gene expression, with TFs modulating mRNA expression and miRNAs acting post-transcriptionally via RNA silencing ( 30 , 35 ). The identified TFs, including GATA3, STAT1, IRF2, NFKB1, RELA, and FOXC1, and miRNAs, such as hsa-mir-335-5p, hsa-mir-4505, hsa-mir-143-3p, hsa-miR-26b-5p, and hsa-miR-146a-5p, are associated with a range of respiratory diseases, including asthma, ARDS, and pulmonary fibrosis, as well as the pathogenesis and exacerbation of sepsis and COVID-19 ( 32 , 35 , 48 – 50 ).…”

“…Both TFs and miRNAs play crucial roles in regulating gene expression, with TFs modulating mRNA expression and miRNAs acting post-transcriptionally via RNA silencing ( 30 , 35 ). The identified TFs, including GATA3, STAT1, IRF2, NFKB1, RELA, and FOXC1, and miRNAs, such as hsa-mir-335-5p, hsa-mir-4505, hsa-mir-143-3p, hsa-miR-26b-5p, and hsa-miR-146a-5p, are associated with a range of respiratory diseases, including asthma, ARDS, and pulmonary fibrosis, as well as the pathogenesis and exacerbation of sepsis and COVID-19 ( 32 , 35 , 48 – 50 ). Intriguingly, many of these miRNAs have also been implicated in various types of cancer, including lung and gastric cancer ( 32 , 35 , 51 ).…”

In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing

“…Some of these studies detected shared key-genes (sKGs) to disclose common pathogenetic processes of SARS-CoV-2 infections with one or two lung diseases including COPD [ 13 ], IPF [ 6 ], COPD and IPF [ 13 ], ILD [ 7 ], asthma [ 18 ], tuberculosis [ 19 ], cystic fibrosis [ 20 ], pneumonia [ 21 ], emphysema [ 13 ], and bronchitis [ 13 ]. Few of these studies recommended sKGs-guided common drug molecules in which molecules (curcumin, triclosan, tamoxifen, deguelin) were recommended for the treatment of SARS-CoV-2 infections with COPD [ 13 ], molecules (tegobuvir, nilotinib, digoxin, proscillaridin, simeprevir, sorafenib, torin 2, rapamycin, vancomycin and hesperidin) with IPF [ 6 ], molecules (suloctidil, estradiol, prenylamine, clioquinol) with asthma [ 18 ], molecules (rituximab, bevacizumab, bosentan, sitaxentan, and macitentana) with tuberculosis [ 19 ], molecules (imiquimod and raloxifene) with cystic fibrosis [ 20 ]. However, so far, there is no study that explored sKGs/sDEGs to disclose common pathogenetic mechanisms and associated drug molecules for SARS-CoV-2 infections and different lung diseases.…”

Investigation of shared genes and regulatory mechanisms associated with coronavirus disease 2019 and ischemic stroke

“…With advances in gene microarray technology and bioinformatics, researchers can quickly detect and analyze the expression data of thousands of genes in a variety of diseases, which can aid in exploring the common pathogenesis of multiple diseases at the genetic level ( 17 , 18 ). In previous studies, the microarray data GSE16561 and GSE22255 have been used to identify crucial genes associated with IS progression ( 19 , 20 ).…”