Post by Nadica (She/Her) on Aug 19, 2024 2:39:00 GMT
SARS-CoV-2 persistence & T cell activity in the female reproductive tract
Project Summary:
A project to test the hypothesis that the female reproductive tract is a preferential site of SARS-CoV-2 persistence and/or a site of immune dysregulation during long COVID. A chronic inflammatory response – possibly in response to SARS-CoV-2 persisting within the tolerogenic environment of the female reproductive tract – that preferentially occurs in women due to genetic or hormonal factors – may contribute to the higher prevalence of long COVID in women as compared to men.
To test this hypothesis the team is adding to the PolyBio-supported LIINC Tissue Program to collect female reproductive tract and gut tissue biopsy samples from pre-menopausal women with and without long COVID. Tissue samples are being analyzed with multiple advanced technologies to determine:
The extent and nature of SARS-CoV-2 persistence in different mucosal tissue compartments, along with the transcriptomes and surface proteomes of infected cells, and the global inflammatory state of surrounding cells.
Features of SARS-CoV-2-specific T cell responses. This includes identification of SARS-CoV-2-specific T cells harboring public T cell receptors, and analysis of their clonal expansion histories.
Project Background:
A growing body of research connects long COVID to the persistence of SARS-CoV-2 in tissue or host cells. Yet mechanisms by which SARS-CoV-2 persistence might impact long COVID disease progression are not yet fully understood. One striking COVID-19 epidemiological observation is that while men are more likely to exhibit severe acute COVID-19, women, particularly premenopausal women, are more likely than men to experience long COVID.
The current project is testing the hypothesis that the higher prevalence of long COVID in women is initiated by persistent SARS-CoV-2 virus, particularly within tolerogenic mucosal sites such as the gut and female reproductive tract, including endometrial tissue. The endometrium may be a preferential site of SARS-CoV-2 persistence because like the gut, it is a site of immune tolerance: in the case of the gut to allow for exposure to gut microbiome and food antigens, and in the case of the endometrium to allow for sperm and a semi-allogenic fetus. The tolerogenic environments of both sites may favor SARS-CoV-2 persistence. Immune cells from the endometrium also have unique features that are affected by female sex hormones, pregnancy status, and menopause, which can influence SARS-CoV-2 persistence. Overall, this project will improve our understanding of the mechanisms underlying long COVID in women.
Project Summary:
A project to test the hypothesis that the female reproductive tract is a preferential site of SARS-CoV-2 persistence and/or a site of immune dysregulation during long COVID. A chronic inflammatory response – possibly in response to SARS-CoV-2 persisting within the tolerogenic environment of the female reproductive tract – that preferentially occurs in women due to genetic or hormonal factors – may contribute to the higher prevalence of long COVID in women as compared to men.
To test this hypothesis the team is adding to the PolyBio-supported LIINC Tissue Program to collect female reproductive tract and gut tissue biopsy samples from pre-menopausal women with and without long COVID. Tissue samples are being analyzed with multiple advanced technologies to determine:
The extent and nature of SARS-CoV-2 persistence in different mucosal tissue compartments, along with the transcriptomes and surface proteomes of infected cells, and the global inflammatory state of surrounding cells.
Features of SARS-CoV-2-specific T cell responses. This includes identification of SARS-CoV-2-specific T cells harboring public T cell receptors, and analysis of their clonal expansion histories.
Project Background:
A growing body of research connects long COVID to the persistence of SARS-CoV-2 in tissue or host cells. Yet mechanisms by which SARS-CoV-2 persistence might impact long COVID disease progression are not yet fully understood. One striking COVID-19 epidemiological observation is that while men are more likely to exhibit severe acute COVID-19, women, particularly premenopausal women, are more likely than men to experience long COVID.
The current project is testing the hypothesis that the higher prevalence of long COVID in women is initiated by persistent SARS-CoV-2 virus, particularly within tolerogenic mucosal sites such as the gut and female reproductive tract, including endometrial tissue. The endometrium may be a preferential site of SARS-CoV-2 persistence because like the gut, it is a site of immune tolerance: in the case of the gut to allow for exposure to gut microbiome and food antigens, and in the case of the endometrium to allow for sperm and a semi-allogenic fetus. The tolerogenic environments of both sites may favor SARS-CoV-2 persistence. Immune cells from the endometrium also have unique features that are affected by female sex hormones, pregnancy status, and menopause, which can influence SARS-CoV-2 persistence. Overall, this project will improve our understanding of the mechanisms underlying long COVID in women.