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Elevated Glucose Levels Favor Sars-Cov-2 Infection and Monocyte Response Through a Hif-1α/Glycolysis Dependent Axis

32 Pages Posted: 21 May 2020 Sneak Peek Status: Review Complete

See all articles by Ana Campos Codo

Ana Campos Codo

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Gustavo Gastão Davanzo

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Lauar Brito Monteiro

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Gabriela Souza

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Stefanie Muraro

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Victor Carregari

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Carlos Biagi

Department of Genetics at Ribeirao Preto Medical School, University of Sao Paulo

Fernanda Crunfli

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Jeffersson Restrepo

Department of Clinical and Toxicological analyses, School of Pharmaceutical Sciences, University of Sao Paulo

Pedro Vendramini

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Guilherme Reis-de-Oliveira

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Karina Santos

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Daniel Teixeira

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Pierina Parise

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Matheus Martini

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Alexandre Borin

Brazilian Biosciences National Laboratory (LNBio)

Lais Coimbra

Brazilian Biosciences National Laboratory (LNBio)

Vinicius Boldrini

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Natalia Brunetti

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Andre Vieira

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Eli Mansour

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Andrei Sposito

Department of Clinical Medicine, School of Medical Sciences, University of Campinas

Helison Carmo

Department of Clinical Medicine, School of Medical Sciences, University of Campinas

Raisa Ulaf

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Ana Bernardes

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Thyago Nunes

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Andre Palma

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Marcus Agrela

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Maria Moretti

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Fabricio Pereira

Hematology and Hemotherapy Center, Campinas State University

Licio Velloso

University of Campinas - Obesity and Comorbidities Research Center

Marco Vinolo

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Andre Damasio

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Jose Modena

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Robson Carvalho

Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP)

Marcelo Mori

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Daniel Martins-de-Souza

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Helder Nakaya

Department of Clinical and Toxicological analyses, School of Pharmaceutical Sciences, University of Sao Paulo

Alessandro Farias

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Pedro Vieira

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

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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/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.

Keywords: COVID-19, SARS-CoV-2, immunometabolism, HIF-1ɑ, glycolysis, diabetes, glucose levels, monocyte

Suggested Citation

Codo, Ana Campos and Davanzo, Gustavo Gastão and Monteiro, Lauar Brito and Souza, Gabriela and Muraro, Stefanie and Carregari, Victor and Biagi, Carlos and Crunfli, Fernanda and Restrepo, Jeffersson and Vendramini, Pedro and Reis-de-Oliveira, Guilherme and Santos, Karina and Teixeira, Daniel and Parise, Pierina and Martini, Matheus and Borin, Alexandre and Coimbra, Lais and Boldrini, Vinicius and Brunetti, Natalia and Vieira, Andre and Mansour, Eli and Sposito, Andrei and Carmo, Helison and Ulaf, Raisa and Bernardes, Ana and Nunes, Thyago and Palma, Andre and Agrela, Marcus and Moretti, Maria and Pereira, Fabricio and Velloso, Licio and Vinolo, Marco and Damasio, Andre and Modena, Jose and Carvalho, Robson and Mori, Marcelo and Martins-de-Souza, Daniel and Nakaya, Helder and Farias, Alessandro and Vieira, Pedro, Elevated Glucose Levels Favor Sars-Cov-2 Infection and Monocyte Response Through a Hif-1α/Glycolysis Dependent Axis. Available at SSRN: https://ssrn.com/abstract=3606770 or http://dx.doi.org/10.2139/ssrn.3606770
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ana Campos Codo

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Gustavo Gastão Davanzo

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Lauar Brito Monteiro

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Gabriela Souza

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Stefanie Muraro

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Victor Carregari

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Carlos Biagi

Department of Genetics at Ribeirao Preto Medical School, University of Sao Paulo

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Fernanda Crunfli

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Jeffersson Restrepo

Department of Clinical and Toxicological analyses, School of Pharmaceutical Sciences, University of Sao Paulo

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Pedro Vendramini

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Guilherme Reis-de-Oliveira

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Karina Santos

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Daniel Teixeira

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University ( email )

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Pierina Parise

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Matheus Martini

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Alexandre Borin

Brazilian Biosciences National Laboratory (LNBio)

Campinas
Brazil

Lais Coimbra

Brazilian Biosciences National Laboratory (LNBio)

Campinas
Brazil

Vinicius Boldrini

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Natalia Brunetti

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Andre Vieira

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Eli Mansour

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Andrei Sposito

Department of Clinical Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Helison Carmo

Department of Clinical Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Raisa Ulaf

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Ana Bernardes

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Thyago Nunes

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Andre Palma

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Marcus Agrela

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Maria Moretti

Department of Internal Medicine, School of Medical Sciences, University of Campinas

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Fabricio Pereira

Hematology and Hemotherapy Center, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Licio Velloso

University of Campinas - Obesity and Comorbidities Research Center ( email )

Brazil

Marco Vinolo

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Andre Damasio

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Jose Modena

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Robson Carvalho

Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University (UNESP) ( email )

Av. Eufrásia Monteiro Petráglia, 900
Jd. Dr. Antonio Petráglia
Franca, Sao Paulo 14409-160
Brazil

Marcelo Mori

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Daniel Martins-de-Souza

Department of Biochemistry and Tissue Biology, Instituteof Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Helder Nakaya

Department of Clinical and Toxicological analyses, School of Pharmaceutical Sciences, University of Sao Paulo ( email )

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Alessandro Farias

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Pedro Vieira (Contact Author)

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, Campinas State University ( email )

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

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