Comorbid COVID-19/Asthma: Common Host Factors Reveal Potential Drug Targets

A network of common host factors exist between asthma and COVID-19, thus allowing for the prediction of drugs with therapeutic potential for managing COVID-19/asthma comorbidity. Such drugs likely include LY294002, wortmannin, PD98059 and heparin. These were among study findings recently published in Computers in Biology and Medicine.

Common respiratory viruses, such as rhinovirus and respiratory syncytial virus, are linked to both asthma exacerbations and coronavirus infection. Such viruses rely on host factors to replicate. With that in mind, researchers for the current study sought to identify host factors that could serve as potential drug targets for patients with comorbid COVID-19 and asthma.

Investigators in China conducted a retrospective review and analysis to identify datasets that would enable them to determine the molecular mechanisms and protein targets shared between SARS-CoV-2 and asthma. In the datasets found, bronchoalveolar lavage fluid was used to screen differential expressed genes. The shared DEGs then went through a series of complex analyses — including protein-protein interaction (PPI) network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis, and drug candidate prediction — to ultimately identify and verify key common host factors between COVID-19 and asthma in the GSE152418 and GSE164805 datasets.

The researchers’ analysis identified 192 overlapping host factors. Of those, significant host factors included FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5; and of these, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were identified by researchers as the key cohost factors for COVID-19 and asthma. The various expression levels of these 5 key cohost factors were uncovered by tissue-specific enrichment analysis, which also showed the potential for therapeutic drugs for comorbid COVID-19 and asthma in LY294002, wortmannin, PD98059 and heparin. The greatest activity in upstream pathways was seen in the H₂O₂, vascular endothelial growth factor (VEGF), interleukin (IL)-1, and wingless/integrated (Wnt) signaling pathways. Statistical significance of the expression of these 5 key common host factors was confirmed by the validation dataset.

Researchers said, “Our research reveals the immune response that neutrophils participate in is the most important biological process of COVID-19/ asthma comorbidity.” Identifying a network of common host factors between COVID-19 and asthma facilitated the prediction of drugs with therapeutic potential, said investigators, noting that “LY294002, wortmannin, PD98059 and heparin may develop as druggable targets against COVID-19/asthma comorbidity.”

Study limitations include the exclusion of whole blood and lung tissue samples of COVID-19 patients.

Reference

Jiang Y, Yan Q, Liu CX, et al. Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid. Comput Biol Med. Published online May 19, 2022. doi:10.1016/j.compbiomed.2022.105601