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

• Grant number: 20/04579-7
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2020 - March 31, 2022
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: Pedro Manoel Mendes de Moraes Vieira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases, AP.JP
• Associated scholarship(s): 20/08744-2 - Risk factors associated with greater severity to COVID-19 and mapping of metabolic pathways required for the anti-SARSCoV-2 response, BP.PD

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)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOARES, JULIANA C.; SOARES, ANDREY C.; ANGELIM, MONARA KAELLE S. C.; PROENCA-MODENA, JOSE LUIZ; MORAES-VIEIRA, PEDRO M.; MATTOSO, LUIZ H. C.; OLIVEIRA JR, OSVALDO N.. iagnostics of SARS-CoV-2 infection using electrical impedance spectroscopy with an immunosensor to detect the spike protei. Talanta, v. 239, MAR 1 2022. (18/18953-8, 18/22214-6, 20/08744-2, 20/04579-7)

PASCOAL, LIVIA BITENCOURT; RODRIGUES, PATRICIA BRITO; GENARO, LIVIA MOREIRA; DOS SANTOS PEREIRA GOMES, ARILSON BERNARDO; TOLEDO-TEIXEIRA, DANIEL AUGUSTO; PARISE, PIERINA LORENCINI; BISPO-DOS-SANTOS, KARINA; SIMEONI, CAMILA LOPES; GUIMARAES, PAULA VERI; BUSCARATTI, LUCAS ILDEFONSO; et al. Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples. GUT MICROBES, v. 13, n. 1, p. 1-9, JAN 1 2021. (20/04558-0, 20/04583-4, 20/02448-2, 20/02312-3, 19/14342-7, 20/04746-0, 17/26908-0, 20/04579-7, 20/04919-2, 19/06372-3, 13/07607-8, 20/02159-0)

SANTOS E SILVA, JUAN CARLO; VASCONCELOS, AMANDA PEREIRA; YONEHARA NOMA, ISABELLA HARUMI; NORONHA, NATALIA YUMI; AQUINO, RODRIGO; GIDDALURU, JEEVAN; DURAO, LUIZ; COSTA-MARTINS, ANDRE GUILHERME; SCHUCH, VIVIANE; MORAES-VIEIRA, PEDRO M.; et al. Gene signatures of autopsy lungs from obese patients with COVID-19. CLINICAL NUTRITION ESPEN, v. 44, p. 475-478, AUG 2021. (19/27139-5, 18/14933-2, 20/04579-7, 19/27146-1)

BRUNETTI, NATALIA S.; DAVANZO, GUSTAVO G.; DE MORAES, DIOGO; FERRARI, ALLAN J. R.; SOUZA, GABRIELA F.; MURARO, STEFANIE PRIMON; KNITTEL, THIAGO L.; BOLDRINI, VINICIUS O.; MONTEIRO, LAUAR B.; VIRGILIO-DA-SILVA, JOO VICTOR; et al. SARS-CoV-2 uses CD4 to infect T helper lymphocytes. eLIFE, v. 12, p. 26-pg., 2023-07-31. (20/04558-0, 15/15626-8, 19/06459-1, 19/04726-2, 19/16116-4, 19/05155-9, 19/13552-8, 16/18031-8, 19/00098-7, 20/04583-4, 16/00194-8, 21/08354-2, 19/17007-4, 19/22398-2, 17/01184-9, 19/14465-1, 20/04579-7, 13/08293-7, 18/14933-2, 17/23920-9, 19/06372-3, 16/24163-4, 16/23328-0, 20/04919-2, 20/04746-0)

VEGA, MAITE DUHALDE; OLIVERA, DANIELA; DAVANZO, GUSTAVO GASTAO; BERTULLO, MAURICIO; NOYA, VERONICA; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; CASTRO, ICARO; AREVALO, ANA PAULA; CRISPO, MARTINA; et al. PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical beta-coronavirus disease. SCIENCE ADVANCES, v. 8, n. 38, p. 13-pg., 2022-09-23. (20/04558-0, 20/04579-7)

CODO, ANA CAMPOS; DAVANZO, GUSTAVO GASTAO; MONTEIRO, LAUAR DE BRITO; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; VIRGILIO-DA-SILVA, JOAO VICTOR; PRODONOFF, JULIANA SILVEIRA; CARREGARI, VICTOR CORASOLLA; OLIVEIRA DE BIAGI JUNIOR, CARLOS ALBERTO; CRUNFLI, FERNANDA; et al. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1 alpha/Glycolysis-Dependent Axis. Cell Metabolism, v. 32, n. 3, p. 15-pg., 2020-09-01. (19/00098-7, 20/04558-0, 20/04522-5, 19/06372-3, 16/18031-8, 15/15626-8, 16/23328-0, 17/01184-9, 20/04919-2, 20/04583-4, 20/04579-7, 18/22505-0, 20/04746-0)

SACCON, TATIANA DANDOLINI; MOUSOVICH-NETO, FELIPPE; LUDWIG, RAISSA GUIMARAES; CARREGARI, VICTOR CORASOLLA; DOS ANJOS SOUZA, ANA BEATRIZ; DOS PASSOS, AMANDA STEPHANE CRUZ; MARTINI, MATHEUS CAVALHEIRO; BARBOSA, PRISCILLA PASCHOAL; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; et al. SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner. NATURE COMMUNICATIONS, v. 13, n. 1, p. 15-pg., 2022-09-29. (20/08716-9, 20/04558-0, 19/05155-9, 21/10373-5, 13/07607-8, 20/04919-2, 20/04746-0, 17/01184-9, 17/23920-9, 16/24163-4, 16/00194-8, 18/21635-8, 19/00098-7, 20/05040-4, 17/08264-8, 20/04579-7, 19/26119-0, 19/04726-2, 20/04583-4, 20/15959-5)