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Risk factors associated with greater severity to COVID-19 and mapping of metabolic pathways required for the anti-SARSCoV-2 response

Grant number: 20/08744-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2020
Effective date (End): March 31, 2022
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Pedro Manoel Mendes de Moraes Vieira
Grantee:Monara Kaélle Sérvulo Cruz Angelim
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:20/04579-7 - 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, AP.R

Abstract

The ongoing COVID-19 (Coronavirus Disease 2019) pandemic caused by the new Severe Acute Respiratory Syndrome virus (SARS-CoV-2), has already been confirmed in more than 8 million people on all continents and has been responsible for more than 450 thousand deaths worldwide (World Health Organization - WHO, official data of June 19, 2020). This virus mainly affects the respiratory system, where more than 20% of those infected develop hypoxemia and Pneumonia. To date, there is no approved pharmacological treatment that is effective in preventing infection or treating patients with COVID-19. The only current treatment for severe cases is ventilation support with still unsatisfactory results.Although the likelihood of contracting SARS-CoV-2 appears similar across age groups, severity and case-fatality rate are increased by up to five times among elderly patients or those with comorbidities such as Obesity, Diabetes, High Blood Pressure and cardiovascular disease. Given that situation, the scientific community have been directed great efforts to elucidate the mechanism of action of the virus in that population to propose effective therapeutic approaches. Recent publications indicate that SARS-CoV-2 especially infects pulmonary epithelial cells and macrophages, altering their metabolism to induce pathways favourable to their replication. Thus, investigating specific metabolic pathways is extremely promising to improve the antiviral response, which implies greater production of interferons by the patient. That said, this project aims to investigate the metabolic pathways that interfere with viral replication and the induction of interferons and to identify the factors responsible for the greater severity of COVID-19 in diabetic and obese patients. Through this study, it is expected to obtain further clarification on the mechanisms related to SARS-CoV-2 infection in order to suggest therapies aimed at controlling the spread of the disease and improving the quality of life of infected individuals. (AU)