An overview of sex hormones in relation to SARS-CoV-2 infection (original) (raw)

The Looming Effects of Estrogen in Covid-19: A Rocky Rollout

Frontiers in Nutrition, 2021

In the face of the Covid-19 pandemic, an intensive number of studies have been performed to understand in a deeper way the mechanisms behind better or worse clinical outcomes. Epidemiologically, men subjects are more prone to severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infections than women, with a similar scenario being also stated to the previous coronavirus diseases, namely, SARS-CoV in 2003 and Middle East Respiratory Syndrome coronavirus diseases (MERS-CoV) in 2012. In addition, and despite that aging is regarded as an independent risk factor for the severe form of the disease, even so, women protection is evident. In this way, it has been expected that sex hormones are the main determinant factors in gender differences, with the immunomodulatory effects of estrogen in different viral infections, chiefly in Covid-19, attracting more attention as it might explain the case-fatality rate and predisposition of men for Covid-19 severity. Here, we aim to provide...

Sex hormones and immune system: Menopausal hormone therapy in the context of COVID-19 pandemic

Frontiers in Immunology

The fatal outcomes of COVID-19 are related to the high reactivity of the innate wing of immunity. Estrogens could exert anti-inflammatory effects during SARS-CoV-2 infection at different stages: from increasing the antiviral resistance of individual cells to counteracting the pro-inflammatory cytokine production. A complex relationship between sex hormones and immune system implies that menopausal hormone therapy (MHT) has pleiotropic effects on immunity in peri- and postmenopausal patients. The definite immunological benefits of perimenopausal MHT confirm the important role of estrogens in regulation of immune functionalities. In this review, we attempt to explore how sex hormones and MHT affect immunological parameters of the organism at different level (in vitro, in vivo) and what mechanisms are involved in their protective response to the new coronavirus infection. The correlation of sex steroid levels with severity and lethality of the disease indicates the potential of using h...

Sex hormones as an emerging weapon to combat COVID-19

Coronavirus disease 2019 (COVID-19) started as an epidemic in Wuhan in 2019 and was declared pandemic by WHO in March 2020. The virus has been identified and named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel coronavirus strain is the causative agent of COVID-19, and continues to rapidly spread worldwide. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that spreads through respiratory droplets and unprotected close contact.(1)“COVID‑19 outbreak, which has caused >95 millions confirmed infections and >2 million coronavirus related deaths, is one of the most disastrous worldwide crises in recent years. Several methods have been used to examine SARS-CoV-2 infections.” i.e. RT-qPCR for viral RNA detection, and rapid screening procedures for antibody or virus detection. COVID-19 shows an incubation period of 3–7 days globally. Approximately 80% of the cases remain mild or asymptomatic, 15% are severe and 5% infectious cases turn to cri...

The gendered impact of coronavirus disease (COVID-19): do estrogens play a role?

The European Journal of Contraception & Reproductive Health Care, 2020

Objective: Although sex-disaggregated data for COVID-19 show equal numbers of cases between men and women, there seem to be sex differences in mortality rate and vulnerability to the disease: more men than women are dying. Methods: We have explored the potential role of estrogens in this COVID-19 gendered impact. Results: Estrogens stimulate the humoral response to viral infections, while testosterone and progesterone give an immune suppression of both innate and cell-mediated immune responses. We hypothesise that estrogens, in particular estradiol but also synthetic estrogen such as ethinylestradiol, could protect women from the most serious complications of COVID-19. The use of medications that keep hormonal levels high and stable, such as combined hormonal contraceptive, could therefore play a protective role. These potential benefits overtake the thrombotic risk in healthy women. As stated by the World Health Organization, all modern methods of contraception were safe to use during the COVID-19 pandemic.

Immunity, Sex Hormones, and Environmental Factors as Determinants of COVID-19 Disparity in Women

Frontiers in Immunology, 2021

The current coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in a major global pandemic, causing extreme morbidity and mortality. Few studies appear to suggest a significant impact of gender in morbidity and mortality, where men are reported at a higher risk than women. The infectivity, transmissibility, and varying degree of disease manifestation (mild, modest, and severe) in population studies reinforce the importance of a number of genetic and epigenetic factors, in the context of immune response and gender. The present review dwells on several contributing factors such as a stronger innate immune response, estrogen, angiotensin-converting enzyme 2 gene, and microbiota, which impart greater resistance to the SARS-CoV-2 infection and disease progression in women. In addition, the underlying importance of associated microbiota and certain environmental factors in gender-based disparity pertaining to the mortality an...

Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer

Cancers, 2020

The novel coronavirus disease 2019 (COVID-19) shows a wide spectrum of clinical presentations, severity, and fatality rates. The reason older patients and males show increased risk of severe disease and death remains uncertain. Sex hormones, such as estradiol, progesterone, and testosterone, might be implicated in the age-dependent and sex-specific severity of COVID-19. High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2). Data from patients with prostate cancer treated with androgen-deprivation therapy seem to confirm this hypothesis. Clinical studies on TMPRSS2 inhibitors, such as camostat, nafamostat, and bromhexine, are ongoing. Antiandrogens, such as bicalutamide and enzalutamide, are also under investigation. Conversely, other studies suggest that the immune modulating properties of androgens could pro...

Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis

Maturitas, 2021

Objective To investigate sex-and gender-based differences linked to SARS-COV-2 infection and to explore the role of hormonal therapy (HT) in females. Study design Data from the self-administered, cross-sectional, web-based EPICOVID19 survey of 198,822 adults living in Italy who completed an online questionnaire during the first wave of the epidemic in Italy (April-May 2020) were analyzed. Main outcomes measures Multivariate binary logistic and multinomial regression models were respectively used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for positive nasopharyngeal swab (NPS) test results and severe SARS-CoV-2 infection. Results The data from 6,873 participants (mean age 47.9 ± 14.1 years, 65.8% females) who had a known result from an NPS test were analyzed. According to the multivariate analysis, females had lower odds of a positive result from the NPS test (aOR 0.75, 95%CI 0.66-0.85) and of having a severe infection (aOR 0.46, 95%CI 0.37-0.57) than did their male counterparts. These differences were greater with decreasing age in both sexes. In addition, females aged ≥60 years receiving HT (N = 2,153, 47.6%) had a 46% lower probability of having a positive NPS test (aOR 0.54, 95%CI 0.36-0.80) than their same-aged peers who had never used HT; there were no differences in the younger age groups with respect to HT status. Conclusion Female sex was associated with an age-dependent lower risk of having a severe SARS-CoV-2 infection than their male counterparts. Age seemed to modify the relationship between HT status and infection: while the two were not related among younger participants, it was negative in the older ones. Future prospective studies are needed to elucidate the potential protective role sex hormones may play. Trial registration ClinicalTrials.gov NCT04471701.

The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection

Frontiers in Physiology, 2021

The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angiotensin converting enzyme 2 (ACE2), and regulation of both immune activity and ACE2 by sex steroids. From this flows understanding of why lung and other organs are more susceptible to COVID19 damage in men, and how their distinct immunological landscapes need to be acknowledged to guide prognosis and treatment. Pregnancy, menopause, and hormone replacement therapy bring changed hormonal environments and the need for better stratification in COVID19 studies. We end by noting clinical trials based ...

Sex-derived attributes contributing to SARS-CoV-2 mortality

American Journal of Physiology-Endocrinology and Metabolism, 2020

Epidemiological data in COVID-19 mortality indicate that men are more prone to die of SARS-CoV-2 infection than women, but biological causes for this sexual dimorphism are unknown. We discuss the prospective behavioral and biological differences between the sexes that could be attributed to this sex-based differentiation. The female sex hormones and the immune stimulatory genes, including Toll-like receptors, interleukins, and micro-RNAs present on X-chromosome, may impart lesser infectivity and mortality of the SARS-CoV-2 in females over males. The sex hormone estrogen interacts with the renin-angiotensin-aldosterone system, one of the most critical pathways in COVID-19 infectivity, and modulates the vasomotor homeostasis. Testosterone on the contrary enhances the levels of the two most critical molecules, angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine-type 2 (TMPRSS2), transcriptionally and posttranslationally, thereby increasing viral load and delayi...

The Importance of Female Reproductive Changes in COVID-19 and Vaccine Administration: A Narrative Review

Journal of obstetrics, gynecology and cancer research, 2023

The COVID-19 pandemic has disrupted people's lives all over the world, and vaccination is one of the best ways to eradicate this pandemic and save people's lives. Despite this, vaccines have many known and unknown side effects like fever, fatigue, headache, etc. Fertility is an important aspect of human life, but there are too many concerns about its relationship with COVID-19 and its vaccines. Women are complaining of menstrual irregularities like postmenopausal bleeding, heavy menstrual bleeding, polymenorrhea and fertility concerns after receiving the second dose of the COVID-19 vaccine. The immunologic reactions between vaccine ingredients and the immune system of the body seem to be responsible for this global issue. Angiotensinconverting enzyme 2 (ACE2) and Basigin (BSG) are the receptors for SARS-COV-2. ACE2 is expressed in the human respiratory system, kidney, vagina, uterus and particularly widely in the ovaries, and BSG is expressed in the uterus, ovary stroma and granulosa cells. Therefore, SARS-COV-2 can invade the target cells by attachment to ACE2 and BSG and modulate their expression, and through these probable mechanisms, it can disturb female reproduction and menstruation. According to this accumulated evidence, in this study we aimed at summarizing the recent studies with a focus on probable mechanisms by which SARS-COV-2 and COVID-19 vaccines affect menstruation irregularities and reproduction complications.