Deciphering the interplay between immunoendocrine responses and gastrointestinal manifestations in the worsening of COVID-19

• Grant number: 25/01983-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Cristina Ribeiro de Barros Cardoso
• Grantee: Firmino Martins dos Santos Neto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/03257-4 - The interplay between SARS-CoV-2 infection and dysregulated gut immunity, AP.TEM

Abstract

The COVID-19 pandemic has affected millions of people worldwide, leading to a myriad of clinical manifestations and disease worsening, especially in older non-vaccinated patients, from male sex, an in those presenting comorbidities such as diabetes. In acute disease, gastrointestinal (GI) symptoms can be present and also persist in the convalescence phase, together with other sequelae post infection. Interestingly, gut dysbiosis is presented by type 2 diabetes patients with COVID-19 and pre-existing gut barrier dysfunction in subjects with comorbidities such as diabetes may be associated with multisystemic complications of severe COVID-19. Thus, the resulting dysbiosis makes these subjects more prone to persistent, low-grade systemic inflammation and impaired immune regulation. On the other hand, metabolic disturbances and gut dysbiosis are linked to hyperandrogenism in female mice, while hypogonadism changes gut microbiota in male hosts. Most notably, along with diabetes, male sex is also a significant risk factor for COVID-19 severity. In our previously published findings, we demonstrated that testosterone levels in male diabetes patients are significantly reduced even prior to SARS-CoV-2 infection, with a further pronounced decline during disease progression. Therefore, this project aims to investigate the intricate association between immunoendocrine interactions and gut barrier disruption, as severity determinants of COVID-19.