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LTB4-Driven Inflammation and Increased Expression of ALOX5 / ACE2 During Severe COVID-19 in Individuals With Diabetes

2021; American Diabetes Association; Volume: 70; Issue: 9 Linguagem: Inglês

10.2337/db20-1260

1939-327X

Ícaro Bonyek-Silva, Antônio Fernando Araújo Machado, Thiago Cerqueira‐Silva, Sara Nunes, Márcio Rivison Silva Cruz, Jéssica Silva, Reinan Lima Santos, Aldina Barral, Pablo Rafael Silveira Oliveira, Ricardo Khouri, C. Henrique Serezani, Cláudia Brodskyn, Juliana Caldas, Manoel Barral‐Netto, Viviane Boaventura, Natália Machado Tavares,

Long-Term Effects of COVID-19

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.