Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2022 Sep 23;13:988479. doi: 10.3389/fimmu.2022.988479. eCollection 2022.
The 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.
Two 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.
We 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.
We 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.
冠状病毒病（COVID-19）大流行对全球卫生系统构成了重大挑战。越来越多的证据表明，哮喘表型和合并症是 COVID-19 症状严重程度的主要危险因素。然而，COVID-19 与哮喘之间关联的分子机制尚不清楚。因此，我们进行了生物信息学和系统生物学分析，以确定 COVID-19 患者和哮喘患者的常见途径和分子生物标志物，以及治疗 COVID-19 和哮喘患者的潜在分子机制和候选药物。
通过交集分析从 GSE171110 和 GSE143192 数据集获得两组差异表达基因（DEGs），以鉴定共同的枢纽基因、共享途径和候选药物。此外，还利用鼠模型探索了这些枢纽基因在哮喘和肺炎症/损伤中的表达水平和相关性。
我们在哮喘和 COVID-19 数据集之间发现了 157 个共同的 DEGs。使用各种组合统计方法和生物信息学工具构建了蛋白质-蛋白质相互作用网络，揭示了几个枢纽基因和关键模块。其中 6 个枢纽基因在鼠哮喘肺中显著上调，并与 IL-5、IL-13 和 MUC5AC 呈正相关，这些都是过敏性哮喘的关键介质。基因本体论和途径分析揭示了哮喘和 COVID-19 进展之间的共同关联。最后，我们使用枢纽基因鉴定了转录因子-基因相互作用、DEG- microRNA 核心调控网络以及潜在的药物和化学化合物相互作用。
我们确定了可作为 COVID-19 和哮喘新型生物标志物的 15 个顶级枢纽基因，并发现了几种有前途的候选药物，这些药物可能有助于治疗 COVID-19 和哮喘患者。
