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

Cell Metabolism
Ana Campos CodoPedro M Moraes-Vieira

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.

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Datasets Mentioned

BETA
PXD019157
MT126808.1

Methods Mentioned

BETA
bronchoalveolar lavage
RNA-seq
flow cytometry
PCR
density-gradient centrifugation
scRNA-seq
PCA

Software Mentioned

Enrichr
Progenesis
Prism8
Excel
GraphPad Prism
Python
NetworkAnalyst
Corrplot R
Algorithms
R

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