Translational study on the role of pro-resolution lipids as mediators of tolerance to SARS-CoV-2 infection

The pandemic of the new coronavirus, COVID-19, caused by the SARS-CoV-2 virus, has been causing an unprecedented number of hospitalizations and deaths worldwide, which seems to be far from over. The high transmissibility and the absence of vaccines and effective therapies against this infection, combined with the need for mass intubation of patients in respirators in ICU beds, composes a tragic scenario where the consequence has been the collapse of public health systems in several countries. countries. The first reports and clinical studies published recently, clearly point to diabetes (type 1 or 2), as one of the main risk factors for death from COVID-19. For these reasons, it is essential and urgent that we deepen our understanding of the mechanisms that make the diabetic, a patient more vulnerable to the severe form of this disease. The first studies investigating the pathology of the disease, indicate that the condition suggests an ineffective process of resolving the inflammatory process caused by the virus. Pro-resolution lipid mediators (MLPRs) are lipids that have the function of resolving inflammation, and are known to be reduced in obese / diabetic patients, as well as in murine models of obesity. For this reason, our hypothesis is that diabetic patients are more vulnerable to the inflammatory process due to SARS-CoV-2 infection, due to their low levels of MLPRs and, therefore, due to their low ability to resolve inflammation in the pathways. aerial views of patients. In this project, we propose a translational research strategy, aiming to achieve 3 main objectives: (1) to determine the correlation between the plasma levels of MLPRs with inflammatory and clinical markers of patients infected with the new coronavirus; (2) identify, through in vitro assays, MLPRs with the greatest protective effect on the pulmonary epithelium infected with SARS-CoV-2; and (3) to evaluate, in an in vivo study with a murine model of metabolic syndrome, the protective effect of MLPR on the inflammatory process and lung damage caused by SARS-CoV-2 infection.