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Prospective evaluation of lipid mediators production on the immune response against COVID-19: search for biomarkers and new therapeutic targets in the evolution of the disease

Abstract

The world is experiencing a pandemic caused by SARS-COV-2. Patients suffering COVID-19 can experience moderate to severe complications, especially males, the elderly and/or those presenting with underlying diseases. Severe cases present the "cytokine storm", with an exacerbated inflammatory response in the lung, the most affected organ. On the other hand, most infections are oligo- or asymptomatic. This project seeks to identify molecular factors of susceptibility and resistance to present clinical disease, as well as biomarkers of clinical evolution in COVID-19. Towards this end, we will investigate the inflammatory profile of patients by detecting and quantifying lipid mediators, including eicosanoids, steroid hormones and compounds derived from sphingolipids and ceramides, to seek a possible association with the clinical outcomes of COVID-19, and with components of the immune response such as cytokines, chemokines and N-glycans profiles of IgG Fcs, which may be causally related with lipid mediator profiles. In a case-control study, control participants (non-infected and asymptomatic) and patients treated at Hospital São Paulo in the city of Ribeirão Preto will be recruited; Patients will be evaluated clinically and laboratory by physicians responsible for care; proof of infection with SARS-COV-2 will be determined in all participants. Plasma and leukocytes (buffy coat) will be obtained from blood. Protein inflammatory mediators will be quantified in plasma, as well as eicosanoids, steroid hormones, sphingolipid-derived compounds and ceramides and profiles of N-glycans in the IgGs Fcs will be detected through the use of mass spectrometry. Buffy coat cells will be frozen in Trizol, for later RNA extraction and analysis of gene expression. Therefore, a multidisciplinary, 'omic' approach will identify components of inflammatory process in COVID-19. With the results, we expect to improve understanding of the pathophysiology of COVID-19, to establish markers of disease evolution, as well as new targets for the clinical management of severe COVID-19, since those currently employed are not satisfactory. (AU)

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Scientific publications
(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)
DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; MARUYAMA, SANDRA REGINA; SORGI, CARLOS ARTERIO; DE SOUSA RUSSO, ELISA MARIA; MORAIS FERNANDES, ANA PAULA; DE BARROS CARDOSO, CRISTINA RIBEIRO; FACCIOLI, LUCIA HELENA; DIAS-BARUFFI, MARCELO; DEPERON BONATO, VANIA LUIZA. COVID-19: Integrating the Complexity of Systemic and Pulmonary Immunopathology to Identify Biomarkers for Different Outcomes. FRONTIERS IN IMMUNOLOGY, v. 11, . (20/05207-6, 17/21629-5, 20/05270-0)

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