Atividade da enzima indoleamina-2,3-dioxigenase na resposta imune em Covid-19

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, began in December 2019, and already is the biggest sanitary crisis of the past century. In the most severe cases, COVID-19 generates a strong and uncontrolled inflammatory response, that, aside from being unable to hamper viral replication, damages the host, particularly at the lungs. IDO is an enzyme responsible for converting tryptophan in kynurenine and has an immunemodulatory activity that is related to T regulatory cells differentiation and suppression of effector T cell responses, stablishing, therefore, an immunesuppressive environment. This study aims to elucidate the role of IDO and kynurenine in the immunepathogenesis of COVID- 19. Blood, serum and plasma samples were obtained from severe and nonsevere COVID-19 patients, from which kynurenine and tryptophan were extracted, then measured by HPLC and finally compared to the levels found in healthy controls. Through immunohistochemistry, IDO was detected in lung necropsy samples from patients with COVID-19. The results showed increase of kynurenine levels in severe patients, particularly of those who perished, in comparison to those found in non-severe patients. Kynurenine levels and KYN/TRP ratio were positively correlated with the augmentation of inflammatory markers and prognostic factors, such as IL-6 and neutrophil/lymphocyte ratio, suggesting that the increase in IDO activity is a driven by the uncontrollable inflammation typical of severe COVID-19. Kynurenine and KYN/TRP ration were also efficient as severity predictors but not clinical outcome. Increased IDO expression was also found on the lung of deceased COVID-19 patients, in relation to that of healthy mice controls. These results display increase of IDO activity in severe COVID-19.