tetano
Editor, Senior Moderator
Diabetes
. 2021 Jun 15;db201260.
doi: 10.2337/db20-1260. Online ahead of print.
LTB [SUB]4[/SUB]-Driven Inflammation and Increased Expression of ALOX5/ ACE2 During Severe COVID-19 in Individuals With Diabetes
Icaro Bonyek-Silva[SUP] 1 2 [/SUP], Antônio Fernando Araújo Machado[SUP] 3 [/SUP], Thiago Cerqueira-Silva[SUP] 1 2 [/SUP], Sara Nunes[SUP] 1 2 [/SUP], Márcio Rivison Silva Cruz[SUP] 4 [/SUP], Jéssica Silva[SUP] 1 2 [/SUP], Reinan Lima Santos[SUP] 1 5 [/SUP], Aldina Barral[SUP] 1 2 6 [/SUP], Pablo Rafael Silveira Oliveira[SUP] 7 [/SUP], Ricardo Khouri[SUP] 1 2 [/SUP], C Henrique Serezani[SUP] 8 [/SUP], Cláudia Brodskyn[SUP] 1 2 5 [/SUP], Juliana Ribeiro Caldas[SUP] 4 9 10 [/SUP], Manoel Barral-Netto[SUP] 1 2 6 [/SUP], Viviane Boaventura[SUP] 1 2 [/SUP], Natalia Machado Tavares[SUP] 11 2 6 [/SUP]
Affiliations
Abstract
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 B[SUB]4[/SUB] (LTB[SUB]4[/SUB]) pathway (ALOX5). We found that diabetes activates the LTB[SUB]4[/SUB] 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 (FiO[SUB]2[/SUB]) and arterial partial pressure of oxygen/FiO[SUB]2[/SUB] 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 LTB[SUB]4[/SUB] 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 LTB[SUB]4[/SUB] and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.
. 2021 Jun 15;db201260.
doi: 10.2337/db20-1260. Online ahead of print.
LTB [SUB]4[/SUB]-Driven Inflammation and Increased Expression of ALOX5/ ACE2 During Severe COVID-19 in Individuals With Diabetes
Icaro Bonyek-Silva[SUP] 1 2 [/SUP], Antônio Fernando Araújo Machado[SUP] 3 [/SUP], Thiago Cerqueira-Silva[SUP] 1 2 [/SUP], Sara Nunes[SUP] 1 2 [/SUP], Márcio Rivison Silva Cruz[SUP] 4 [/SUP], Jéssica Silva[SUP] 1 2 [/SUP], Reinan Lima Santos[SUP] 1 5 [/SUP], Aldina Barral[SUP] 1 2 6 [/SUP], Pablo Rafael Silveira Oliveira[SUP] 7 [/SUP], Ricardo Khouri[SUP] 1 2 [/SUP], C Henrique Serezani[SUP] 8 [/SUP], Cláudia Brodskyn[SUP] 1 2 5 [/SUP], Juliana Ribeiro Caldas[SUP] 4 9 10 [/SUP], Manoel Barral-Netto[SUP] 1 2 6 [/SUP], Viviane Boaventura[SUP] 1 2 [/SUP], Natalia Machado Tavares[SUP] 11 2 6 [/SUP]
Affiliations
- PMID: 34417262
- DOI: 10.2337/db20-1260
Abstract
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 B[SUB]4[/SUB] (LTB[SUB]4[/SUB]) pathway (ALOX5). We found that diabetes activates the LTB[SUB]4[/SUB] 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 (FiO[SUB]2[/SUB]) and arterial partial pressure of oxygen/FiO[SUB]2[/SUB] 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 LTB[SUB]4[/SUB] 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 LTB[SUB]4[/SUB] and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.