Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

Front Pharmacol. 2021 Dec 23:12:718874. doi: 10.3389/fphar.2021.718874. eCollection 2021.

Abstract

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited. Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, |LogFC|≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction. Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions. Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.

Keywords: COPD; COVID-19; bioinformatics analyses; comorbidity; host factor interaction networks.

Grants and funding

This research was funded by grants from the “Double First-Class” and High-level University Discipline Collaborative Innovation Team Project of Guangzhou University of Chinese Medicine (Grant No. 2021XK16), the Guangdong Provincial Department of Education Innovation Team Project (Grant No. 2018KCXTD007), the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine (Grant No. 20212056), the Key-Area Research and Development Program of Guangdong Province (Grant No. 2020B1111100002), the National Natural Science Foundation of China (Grant Nos. 81973814 and 81904132), the Natural Science Foundation of Guangdong Province (Grant No. 2017A030310129), the Natural Science Foundation of Guangdong Province (Grant No. 2020A1515010589), the scientific research project of Traditional Chinese Medicine Bureau of Guangdong Province (20201092), the Construction Project of Respiratory Department National Clinical Medical Research Center (Grant No. 2110200309), 2018 Guangzhou University of Chinese Medicine National University Student Innovation and Entrepreneurship Training Project (Grant No. 201810572038), 2020 National College Student Innovation and Entrepreneurship Training Project of Guangzhou University of Chinese Medicine (Grant No. 202010572001), the Student Learning Team Incubation Project of Innovation Academy from The First Affiliated Hospital of Guangzhou University of Chinese Medicine (Grant No. 2018XXTD003), and the Technology Research of COVID-19 Treatment and Prevention and Special Project of Traditional Chinese Medicine Application-Research on the platform construction for the prevention and treatment of viral infectious diseases with traditional Chinese medicine (Grant No. 2020KJCXKTYJ-130).