LTB4-Driven Inflammation and Increased Expression of <i>ALOX5</i>/<i>ACE2</i> During Severe COVID-19 in Individuals With Diabetes
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- Icaro Bonyek-Silva
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Antônio Fernando Araújo Machado
- Salvador University, Salvador, Bahia, Brazil
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- Thiago Cerqueira-Silva
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Sara Nunes
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Márcio Rivison Silva Cruz
- Salvador University, Salvador, Bahia, Brazil
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- Jéssica Silva
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Reinan Lima Santos
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Aldina Barral
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Pablo Rafael Silveira Oliveira
- Institute of Biological Sciences, Federal University of Bahia, Salvador, Bahia, Brazil
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- Ricardo Khouri
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- C. Henrique Serezani
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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- Cláudia Brodskyn
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Juliana Ribeiro Caldas
- Salvador University, Salvador, Bahia, Brazil
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- Manoel Barral-Netto
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Viviane Boaventura
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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- Natalia Machado Tavares
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
説明
<jats:p>Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19–related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 70 (9), 2120-2130, 2021-06-15
American Diabetes Association