Research Grants 20/13370-4 - Pneumologia, Doenças pulmonares intersticiais - BV FAPESP
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COVID-19-induced fibrosing interstitial pneumonitis

Grant number: 20/13370-4
Support Opportunities:Regular Research Grants
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Alexandre Todorovic Fabro
Grantee:Alexandre Todorovic Fabro
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers: Andrea de Cássia Vernier Antunes Cetlin ; Marcel Koenigkam Santos ; Marcelo Bezerra de Menezes ; Robson Francisco Carvalho ; Sirlei Siani Morais ; Tales Rubens de Nadai

Abstract

Fibrosing interstitial pneumonitis (FIP) can be defined as an attempt to repair the injured lung tissue, with some or extensive extracellular matrix deposition, causing lung parenchyma disarrangement and septal thickening. The regulatory mechanisms involved in fibrogenesis are complex and with several molecules. FIP can be the common end result to many different lung diseases (for instance idiopathic pulmonary fibrosis) or be related to chronic viral inflammations, such as the new 2019 Coronavirus Disease (COVID-19), caused by the SARS-CoV-2 virus. Some patients infected with this disease develop the acute respiratory distress syndrome, which is characterized by acute and diffuse inflammatory damage to the pulmonary alveoli. Histopathologically, this condition is known as diffuse alveolar damage, which consists of permanent damage to epithelial and endothelial cells with consequent hyaline membrane formation. In addition, this condition is characterized by exacerbated myofibroblastic proliferation with subsequent extracellular matrix deposition, resulting in parenchyma remodeling and future FIP, which can frequently be the COVID-19 outcome. Thus, fibroblasts and myofibroblasts are the main factors within the fibrogenesis process and the comprehension of regulatory mechanisms and the genes involved in this process are essential for its complete understanding. At the same time, this knowledge translationally integrated with clinical-radio-laboratory profile could determine the patients' phenotype in relation to the stage of fibrosing interstitial pneumonitis . With this in mind and due to the COVID-19 great socioeconomic impact, the transcriptomic profile of infected lung tissue together with the characterization of fibrotic pulmonary microenvironment will enable the identification of a wide range of potential biomarkers that may predict fibrosing interstitial pneumonitis in these patients. Therefore, the main purpose of this project is to determine the molecular profile and potential biomarker of pulmonary myofibroblastic microenvironment post-COVID19, characterizing patients in different phenotypes according to the PIF degree, after translational screening of COVID-19 candidates through minimally invasive autopsy. (AU)

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