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SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle.

ABSTRACT: OBJECTIVE:To determine the susceptibility of the endometrium to infection by-and thereby potential damage from-SARS-CoV-2. DESIGN:Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. SETTING:Infertility research department affiliated with a public hospital. PATIENT(S):Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. RESULT(S):Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. ACE2, TMPRSS4, CTSB, CTSL, BSG, and MX1 expression increased with age, especially in early phases of the cycle. CONCLUSION(S):Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age. Further, TMPRSS4, along with BSG-mediated viral entry into cells, could imply a susceptible environment for SARS-CoV-2 entry via different mechanisms. Additional studies are warranted to determine the true risk of endometrial infection by SARS-CoV-2 and implications for fertility treatments.

SUBMITTER: Henarejos-Castillo I

PROVIDER: S-EPMC7298504 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle.

Henarejos-Castillo Ismael I Sebastian-Leon Patricia P Devesa-Peiro Almudena A Pellicer Antonio A Diaz-Gimeno Patricia P

Fertility and sterility 20200617 2

<h4>Objective</h4>To determine the susceptibility of the endometrium to infection by-and thereby potential damage from-SARS-CoV-2.<h4>Design</h4>Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets.<h4>Setting</h4>Infertility research department affiliated with a public hospital.<h4>Patient(s)</h4>Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle.<h4>Intervention(s)</h4>None.<h4>Ma ...[more]

PMID: 32641214

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Project description:BackgroundDespite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated.ObjectiveThis study aimed to examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics.Study designThis study prospectively observed 3858 premenopausal women in the Nurses' Health Study 3 living in the United States or Canada who received biannual follow-up questionnaires between January 2011 and December 2021 and completed additional monthly and quarterly surveys related to the COVID-19 pandemic between April 2020 and November 2021. History of positive SARS-CoV-2 test, COVID-19 vaccination status, and vaccine type were self-reported in surveys conducted in 2020 and 2021. Current menstrual cycle length and regularity "before COVID-19" were reported at baseline between 2011 and 2016, and current menstrual cycle length and regularity "after COVID-19" were reported in late 2021. Pre- to post-COVID change in menstrual cycle length and regularity was calculated between reports. Logistic or multinomial logistic regression models were used to assess the associations between SARS-CoV-2 infection and COVID-19 vaccination and change in menstrual cycle characteristics.ResultsThe median age at baseline and the median age at end of follow-up were 33 years (range, 21-51) and 42 years (range, 27-56), respectively, with a median follow-up time of 9.2 years. This study documented 421 SARS-CoV-2 infections (10.9%) and 3527 vaccinations (91.4%) during follow-up. Vaccinated women had a higher risk of increased cycle length than unvaccinated women (odds ratio, 1.48; 95% confidence interval, 1.00-2.19), after adjusting for sociodemographic and behavioral factors. These associations were similar after in addition accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0-6 months: odds ratio, 1.67 [95% confidence interval, 1.05-2.64]; 7-9 months: odds ratio, 1.43 [95% confidence interval, 0.96-2.14]; >9 months: odds ratio, 1.41 [95% confidence interval, 0.91-2.18]) and among women whose cycles were short, long, or irregular before vaccination (odds ratio, 2.82 [95% confidence interval, 1.51-5.27]; odds ratio, 1.10 [95% confidence interval, 0.68-1.77] for women with normal length, regular cycles before vaccination). Messenger RNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics.ConclusionCOVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long, or irregular before vaccination. The results underscored the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms.

Dataset Information

SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle.

Publications

SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle.

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