Produção Nacional
Elevated Glucose Levels Favor Sars-Cov-2 Infection and Monocyte Response Through a Hif-1α/Glycolysis Dependent Axis
2020; RELX Group (Netherlands); Linguagem: Inglês
10.2139/ssrn.3606770
ISSN1556-5068
AutoresAna Campos Codo, Gustavo Gastão Davanzo, Lauar de Brito Monteiro, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Victor Corasolla Carregari, Carlos Alberto Oliveira de Biagi, Fernanda Crunfli, Jeffersson Leandro Jimenez Restrepo, Pedro Henrique Vendramini, Guilherme Reis‐de‐Oliveira, Karina dos Santos, Daniel A. Toledo-Teixeira, Pierina Lorencini Parise, Matheus Cavalheiro Martini, Alexandre Borin, Laís D. Coimbra, Vinícius Boldrini, Natália S. Brunetti, André Schwambach Vieira, Eli Mansour, Andrei C. Spósito, Helison Rafael Pereira do Carmo, Raisa G. Ulaf, Ana Flávia Bernardes, Thyago A. Nunes, André C. Palma, Marcus V. Agrela, Maria Luíza Moretti, Fabrício Pereira, Lı́cio A. Velloso, Marco Aurélio Ramirez Vinolo, André Damásio, José Luiz Proença‐Módena, Robson Francisco Carvalho, Marcelo A. Mori, Daniel Martins‐de‐Souza, Helder I. Nakaya, Alessandro Farias, Pedro M. Moraes‐Vieira,
Tópico(s)COVID-19 Clinical Research Studies
ResumoCOVID-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/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-1 ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
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