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

• Grant number: 20/07455-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): September 01, 2020
• Effective date (End): August 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Luiz Osório Silveira Leiria
• Grantee: Ester de Andrade Barreto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 20/05040-4 - Translational study on the role of specialised pro-resolving lipid mediators in the tolerance against CARS-CoV-2 infection, AP.R

Abstract

The novel coronavirus disease pandemic, caused by the SARS-CoV-2 virus, is 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 intubation of patients on ventilators in ICU beds, composes a tragic scenario where the consequence has been the collapse of public health systems in several 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 patient more vulnerable to the severe form of this disease. The first studies investigating the pathology of the disease 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 they are 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 trigged by SARS-CoV-2 infection, due to their low levels of MLPRs and therefore, due to their low capacity to resolve inflammation in the airways of patients. In this project, we propose a translational research strategy, aiming to achieve three main objectives: (1) to determine the correlation between MLPR plasma levels with clinical inflammatory markers and symptoms of patients infected with the new coronavirus; (2) identify, through in vitro tests, the MLPRs with the highest protective effect on the pulmonary epithelium infected with SARS-CoV-2; and (3) to evaluate, in an in vivo study, a murine model of metabolic syndrome, the protective effect of MLPR on the inflammatory process and lung damage caused by SARS-CoV-2 infection. (AU)