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

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

Cell metabolism (2020-07-23)
Ana Campos Codo, Gustavo Gastão Davanzo, Lauar de Brito Monteiro, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, João Victor Virgilio-da-Silva, Juliana Silveira Prodonoff, Victor Corasolla Carregari, Carlos Alberto Oliveira de Biagi Junior, Fernanda Crunfli, Jeffersson Leandro Jimenez Restrepo, Pedro Henrique Vendramini, Guilherme Reis-de-Oliveira, Karina Bispo Dos Santos, Daniel A Toledo-Teixeira, Pierina Lorencini Parise, Matheus Cavalheiro Martini, Rafael Elias Marques, Helison R Carmo, Alexandre Borin, Laís Durço Coimbra, Vinícius O Boldrini, Natalia S Brunetti, Andre S Vieira, Eli Mansour, Raisa G Ulaf, Ana F Bernardes, Thyago A Nunes, Luciana C Ribeiro, Andre C Palma, Marcus V Agrela, Maria Luiza Moretti, Andrei C Sposito, Fabrício Bíscaro Pereira, Licio Augusto Velloso, Marco Aurélio Ramirez Vinolo, André Damasio, José Luiz Proença-Módena, Robson Francisco Carvalho, Marcelo A Mori, Daniel Martins-de-Souza, Helder I Nakaya, Alessandro S Farias, Pedro 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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