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Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential

Olexandr Kamyshnyi1, Victoriya Matskevych2, Tetyana Lenchuk2

  • 1Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|October 10, 2021
PubMed

Insights

Diabetic patients face severe COVID-19 due to immune dysregulation. Targeting the mTOR pathway with drugs like metformin may reduce inflammation and improve outcomes for these patients.

Area of Science:

  • Immunology
  • Endocrinology
  • Virology

Background:

  • COVID-19 pandemic presents significant medical challenges.
  • SARS-CoV-2 infection causes immune dysregulation.
  • Diabetic patients exhibit increased susceptibility to severe COVID-19 due to factors like hyperglycemia and immune dysfunction.

Purpose of the Study:

  • To investigate the molecular mechanisms linking diabetes, immune metabolism, and COVID-19 severity.
  • To explore the role of the mTOR signaling pathway in diabetes-associated COVID-19 complications.
  • To identify potential therapeutic targets for managing severe COVID-19 in diabetic individuals.

Main Methods:

  • Analysis of molecular mechanisms of immune dysregulation in SARS-CoV-2 infection.
  • Examination of the impact of diabetes-induced metabolic changes, particularly hyperglycemia, on lymphocyte immunometabolism.
  • Investigation of the mTOR protein kinase signaling pathway and its modulation by metformin via AMPK activation.

Main Results:

  • High mTOR activity in diabetes promotes pro-inflammatory lymphocyte responses, exacerbating COVID-19 severity.
  • Low mTOR activity favors T-regulatory cell differentiation, potentially mitigating hyperinflammation.
  • Metformin's inhibition of mTOR via AMPK activation presents a potential therapeutic strategy.

Conclusions:

  • Modulating the AMPK/mTOR signaling pathway could be a novel therapeutic approach for COVID-19 in diabetic patients.
  • Inhibiting mTOR may reduce pro-inflammatory signaling and cytokine storm, thereby improving clinical outcomes.
  • Retrospective analyses partially support the efficacy of targeting this pathway in hospitalized diabetic COVID-19 patients.
Keywords:
COVID-19ImmunometabolismLymphocytesMetformin

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