Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis

Cell Metab. 2020 Sep 1;32(3):437-446.e5. doi: 10.1016/j.cmet.2020.07.007. Epub 2020 Jul 17.

Abstract

COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.

Keywords: Covid-19; HIF-1alpha; SARS-CoV-2; diabetes; glycolysis; inflammation; interferon; metabolism; mitochondria; monocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betacoronavirus / physiology*
  • Blood Glucose / metabolism*
  • Cell Line
  • Coronavirus Infections / complications*
  • Coronavirus Infections / metabolism
  • Diabetes Complications / complications*
  • Diabetes Complications / metabolism
  • Diabetes Mellitus / metabolism
  • Female
  • Glycolysis
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Inflammation / complications
  • Inflammation / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Monocytes / virology
  • Pandemics
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Blood Glucose
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2