Abstract
It is well established that pre-existing comorbid conditions such as hypertension, diabetes, obesity, cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), cancers, and chronic obstructive pulmonary disease (COPD) are associated with increased severity and fatality of COVID-19. The increased death from COVID-19 is due to the unavailability of a gold standard therapeutic and, more importantly, the lack of understanding of how the comorbid conditions and COVID-19 interact at the molecular level, so that personalized management strategies can be adopted. Here, using multi-omics data sets and bioinformatics strategy, we identified the pathway crosstalk between COVID-19 and diabetes, hypertension, CVDs, CKDs, and cancers. Further, shared pathways and hub gene-based targets for COVID-19 and its associated specific and combination of comorbid conditions are also predicted towards developing personalized management strategies. The approved drugs for most of these identified targets are also provided towards drug repurposing. Literature supports the involvement of our identified shared pathways in pathogenesis of COVID-19 and development of the specific comorbid condition of interest. Similarly, shared pathways- and hub gene-based targets are also found to have potential implementations in managing COVID-19 patients. However, the identified targets and drugs need further careful evaluation for their repurposing towards personalized treatment of COVID-19 cases having pre-existing specific comorbid conditions we have considered in this analysis. The method applied here may also be helpful in identifying common pathway components and targets in other disease-disease interactions too.
Highlights
The current outbreak of COVID-19 has raised unprecedented obstacles for all and has broken down the healthcare system across several countries [1,2,3,4,5]
We found that 21 genes (TNF, MAPK1, MAPK8, PIK3CA, PIK3CB, PIK3CD, MAPK3, INSR, HK3, HK2, PKM, INS, MTOR, PIK3CG, ADIPOQ, PIK3R1, PIK3R2, PIK3R3, MAPK10, MAPK9, and IKBKB) are shared by both diabetes and COVID-19, of which seven genes
While we analyzed the hubness of these genes using Enrichr PPI Hub Proteins, it was found that IRS1 is the critical gene (Supplementary Figure S1B and Supplementary Table S1). To understand how these 21 genes are involved in COVID-19 pathogenesis, we considered the top 10 pathways enriched by Enrichr
Summary
The current outbreak of COVID-19 has raised unprecedented obstacles for all and has broken down the healthcare system across several countries [1,2,3,4,5]. Heterogeneity is the most striking feature of the outbreak, ranging from no symptoms to critical conditions and death [7,8,9]. The risk of serious disease is increased by age, gender, and comorbidities [10,11,12]. The seriousness of COVID-19 disease progression is associated with several chronic comorbid conditions [13,14]. Worst outcomes have been correlated with comorbidities, which include hypertension, diabetes, cardiovascular diseases (CVDs), obesity, chronic kidney diseases (CKDs), cancers, and chronic obstructive pulmonary disease (COPD), among others [8,15,16,17]. Hypertension, CVDs, and diabetes mellitus are the most common comorbidities in COVID-19 [16,18]. Several post- and long-term complications in COVID-19 survivors are mounting with time [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
