Influence of the female hormone 17-beta-Estradiol on SARS-CoV-2 infection

• Grant number: 20/15738-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2021
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Emily Araujo de Oliveira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The new coronavirus-19 disease (COVID-19), caused by the infectious agent SARS-CoV-2 has become a worldwide public health problem. Data from several countries showed that the number of hospitalizations and deaths caused by the disease were higher in men than in women. This can, in part, be explained by sexual dimorphism, differences based on male and female gender that can influence the immune system and responsiveness to infection. Certain genes such as the one encoding Toll-like receptor 7 (TLR7), which recognizes nucleic acids, the transcription factor Foxp3, and angiotensin-converting enzyme 2 (ACE2) are expressed on the X chromosome. In addition, the female hormone 17²-Estradiol (E2) via estrogen receptors (ER's), can induce IFN-± production by plasmacytoid dendritic cells (pDCs) and IFN-³ production by Th1 helper cells. This project aims to evaluate the influence of the E2 hormone on the evolution of SARS-CoV-2 infection in men and women. To this end, peripheral blood of patients with COVID-19 will be analyzed according to the clinical picture, moderate and severe as to plasma levels of E2, characterization of the phenotypic and functional profile of pDCs, expression of mRNAs of ER's and TLR7/8 in leukocytes. To evaluate the mechanisms involved in dimorphism, the effect of the hormone 17²-Estradiol will be evaluated in vitro, in some populations of peripheral blood mononuclear cells (PBMCs), from patients and healthy individuals regarding: expression profile of interferon-stimulated genes (ISG), antiviral factors, receptors (ERs, TLRs), effector and anti-inflammatory cytokines and type I and II interferons. The findings may contribute to a better understanding of the progression of COVID-19 in male subjects. (AU)