Study of the risk factors associated with greater severity to COVID-19 and mapping of the metabolic pathways required for the anti-SARS-CoV-2 response

Abstract

The pandemic of the new severe acute respiratory syndrome virus (SARS-CoV-2) has already been confirmed in more than 700,000 people on all continents and has been responsible for more than 20,000 deaths worldwide (World Health Organization - official data of March 27, 2020). The only way to treat severe cases is through respiratory support with still unsatisfactory results. To date, there is no efficient pharmacological treatment to modify the natural history of evolution of COVID-19, which results in the mortality of approximately 2% of diagnosed patients, with more than 20% of these progressing with reduced O2 saturation below 94 % and pneumonia. Although the mechanism of action of SARS-CoV-2 is still not completely clear, some groups appear to be more susceptible to the severe form of this infection. Among them are people with pre-existing medical conditions, mainly disorders related to glucose homeostasis (diabetes) and age (hypertension, heart disease, lung disease, cancer and diabetes) and elderly people. SARS-Cov-2 is known to infect pulmonary epithelial cells and macrophages. Several types of virus, when infecting target cells, alter their cellular metabolism, inducing pathways favorable to viral replication. This makes the modulation of specific metabolic pathways extremely promising to induce the production of interferons and improve the antiviral response, leading to decreased viral load. In this project we aim to determine metabolic pathways that interfere with viral replication and with the induction of interferons with therapeutic potential for the treatment of SARS-CoV-2 and to identify the factors responsible for the greater severity of COVID-19 in diabetic patients. With this study we expect to clarify the mechanisms related to SARS-CoV-2 infection so that better treatments are available to the population in order to control the spread of the disease and improve the quality of life of infected individuals. (AU)