Evaluation of Amphiregulin as a prognostic biomarker of severity and its participation in the pathophysiology of COVID-19

• Grant number: 20/05211-3
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2020 - June 30, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: José Carlos Farias Alves Filho
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Alexandre Todorovic Fabro ; Eurico de Arruda Neto ; Fernando de Queiroz Cunha ; Paulo Louzada Junior ; Renê Donizeti Ribeiro de Oliveira ; Thiago Mattar Cunha
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
• Associated scholarship(s): 22/08458-5 - Evaluation of amphregulin as a prognostic biomarker of severity and its participation in the pathophysiology of COVID-19, BP.PD; 21/05428-5 - Development and standardization of experimental models of SARS-CoV-2 virus infection, BP.PD

Abstract

A more recent global health threat or outbreak in the course of the respiratory disease that was named Coronavirus Disease 2019 (COVID-19), is qualified by the virus called SARS-CoV-2. Scientists in basic and clinical areas around the world are having significant effects on the understanding of the pathophysiology and the investigation or effect of drugs with antiviral action and the repositioning of drugs that perform anti-inflammatory action, and there is still no medicine or clinical treatment for patients a COVID-19. However, it is known that progressive respiratory failure causes damage caused by alveolar cells, is caused by viral replication, and excessive local inflammation, is one of the major obstacles to the recovery of critically ill patients with COVID-19. In this sense, the host's defense against infections depends not only on the mechanisms of immune resistance but also on the organism's ability to tolerate the damage that a determined individual promotes. An amphiregulin (AREG) is a central factor that promotes repair and restoration of tissue integrity after tissue damage associated with inflammation. AREG-deficient animals have a substantial impairment of the ability to restore lung function in infection models. In addition, the administration of recombinant AREG enhances the tissue repair process after tissue damage resulting from excessive inflation. Our working hypothesis is that AREG plays a crucial role in repairing and restoring the integrity of lung tissue during a COVID-19 and that treatment with AREG is recombinant during the patients' recovery period. In addition, studies with the hypothesis of determining AREG levels in patients who are still moderately formed can be an important prognostic biomarker of severity in patients. Thus, we propose in the present project to conduct a translational study to investigate an AREG participation in the pathophysiology of COVID-19, using animal models of experimental infection by SARS-CoV-2 and using patients diagnosed with COVID-19. In addition, we intend to assess the potential of AREG as a prognostic biomarker of severity in patients with COVID-19. (AU)