Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

Area of Science:

• Pharmacology
• Infectious Diseases
• Endocrinology

Background:

• COVID-19 has shown complex pathophysiological mechanisms.
• Observational studies suggest metformin may improve COVID-19 outcomes in type 2 diabetes mellitus (T2DM) patients.
• Metformin possesses pleiotropic properties affecting multiple disease pathways.

Purpose of the Study:

• To explore the potential benefits of metformin in managing COVID-19.
• To analyze how metformin's properties align with COVID-19 pathophysiology.
• To highlight metformin's microcirculatory protective effects in severe COVID-19.

Main Methods:

• Review of existing observational studies on metformin and COVID-19.
• Comparison of COVID-19 pathophysiological mechanisms with metformin's known pharmacological actions.
• Analysis of metformin's potential impact on cytokine storm, viral entry, microvascular damage, and fibrosis.

Main Results:

• Metformin may alleviate the cytokine storm associated with severe COVID-19.
• The drug could potentially reduce viral entry into cells.
• Metformin demonstrates protective effects against microvascular damage and secondary fibrosis, crucial in severe COVID-19.

Conclusions:

• Metformin exhibits a unique ability to target multiple COVID-19 pathophysiological processes.
• Its microcirculatory protective effects are particularly relevant given the vascular defects in severe COVID-19.
• Metformin's benefits may extend beyond diabetic patients, acting in a diabetes-independent manner.