Network Meta-Analysis on the Mechanisms underlying Type 2 Diabetes Augmentation of COVID-19 Pathologies

Area of Science:

• Bioinformatics
• Molecular Biology
• Immunology

Background:

• Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, involves ACE2 receptor interaction.
• Non-insulin dependent diabetes mellitus (DM-II) is suspected to exacerbate COVID-19 severity.
• Understanding shared molecular pathways is crucial for co-managing these diseases.

Purpose of the Study:

• To investigate the molecular mechanisms by which DM-II augments COVID-19 complications.
• To identify shared molecules and signaling pathways between DM-II and SARS-CoV-2 infection.
• To explore potential therapeutic targets for simultaneous treatment of both conditions.

Main Methods:

• Utilized QIAGEN Ingenuity Pathway Analysis (IPA) and CLC Genomics Workbench 22 (CLCG-22).
• Analyzed RNA-sequencing data (SRA SRP287500) for differential gene expression.
• Retrieved and analyzed molecules shared between DM-II and SARS-CoV-2 infection using IPA's QIAGEN Knowledge Base (QKB).

Main Results:

• Identified three common molecules (SCL2A2, PPARγ, CPLX8) downregulated by DM-II in both diseases.
• Found that downregulation of these molecules is linked to increased activity of cytokines/chemokines and ACE2.
• Demonstrated that SARS-CoV-2 interaction with ACE2 can induce endothelial cell dysfunction.

Conclusions:

• Shared molecular pathways and common molecules exist between DM-II and SARS-CoV-2 infection.
• The interaction network highlights the role of ACE2 and cytokines/chemokines in disease exacerbation.
• This research may pave the way for novel therapeutic strategies targeting both DM-II and COVID-19.