Estrogen & COVID-19 Severity in Women

Growing clinical evidence reveals that the intensity of COVID-19 infection and incidence of related complications are more prominent in male patients. Current data suggests that men experience a greater risk than women for more severe COVID-19 symptoms and poorer outcomes regardless of their age. These burgeoning findings signal that sex may function as a determinant of COVID-19 infection severity.

While the body of evidence examining sex differences in virus outcomes is lacking, researchers believe the functional modulation of angiotensin-converting enzyme 2 by estrogen may explain disparities in morbidity and mortality. Further reasons for higher male sex-specific COVID-19-related mortality are likely multi-fold and may include lifestyle differences such as higher rates of tobacco smoking and alcohol consumption as well as innate immunity. The mounting evidence suggesting sex-based differences in clinical outcomes emphasizes the need for an assessment of sex-specific hormone activity – in particular, estrogen – in COVID-19 pathogenesis.

Sex-Specific Differences in COVID-19 Outcomes 

A recent study conducted by researchers at the Wake Forest Baptist Medical Center attempts to elucidate the mechanisms underlying these notable differences. Led by Leanne Groban, MD, professor of anesthesiology at Wake Forest School of Medicine, a team of researchers conducted a review of published literature to determine whether sex plays a role in COVID-19 outcomes by examining pre-clinical data on sex-specific hormone activity.

Beneficial Impact of Estrogen

The study’s authors reported that angiotensin-converting enzyme 2 – attached to cell membranes in heart, arteries, kidneys, and intestines – acts as a cellular receptor of the coronavirus responsible for COVID-19 infections and helps the virus gain access to cells of those organ systems. According to the researchers, their review also pointed to estrogen’s impact on ACE2 levels in the heart; the hormone lowered ACE2 levels. This may modulate the severity of COVID-19 in women, while higher levels of ACE2 present in tissues could account for why the disease presents worse in men.

“We know that coronavirus affects the heart and we know that estrogen is protective against cardiovascular disease in women, so the most likely explanation seemed to be hormonal differences between the sexes,” said the lead author of the review, Dr. Groban told ScienceDaily in an interview.

“We hope that our review regarding the role of estrogenic hormones in ACE2 expression and regulation may explain the gender differences in COVID-19 infection and outcomes and serve as a guide for current treatment and the development of new therapies,” Groban said.

An enhanced understanding of the role of estrogenic hormones in ACE2 expression and regulation may not only help uncover potential mechanisms that explain sex differences in COVID-19 clinical outcomes, but also guide future disease management techniques and spur the discovery of novel therapeutic methods.

Gut Bacteria Play a Role in Cancer Tumor Development

In recent years, the role of the gut microbiome in human health and its influence on human diseases – including different types of cancer – has garnered increasing attention. At the same time, its role in cancer treatment has become more apparent with burgeoning evidence of the positive effects associated with gut microbiome modulation, implicating that it may impact patient responses to various cancer therapies.

A growing emphasis on precision medicine makes furthered knowledge and understanding of the microbiome’s influence on immune responses and cancer imperative. The discovery of strategies for manipulating the microbiome, to thereby augment therapeutic responses, relies on understanding the specific factors that influence gut microbiome mechanisms. Although several species of intestinal bacteria have already been linked to the enhanced efficacy of immunotherapies, exactly how the microbiome is able to enhance anti-tumor immunity remains in question.

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Impact of COVID-19 Isolation and Social Distancing on Mental Health

As a method of novel coronavirus disease transmission suppression and an attempt to reduce the risk of infection, social restrictions – such as social distancing and sheltering in place – have been put into place and remain active in the majority of the United States. Such measures have isolated many older adults at home, leaving them with limited contact and social interaction for the duration of the outbreak. As evidenced by global statistics revealing higher death rates among this demographic, the COVID-19 pandemic has been disproportionately affecting older adults.

Current literature suggests that social interaction is an integral component of mental health and wellbeing, while loneliness has been associated with morbidity and mortality in prior research. While the isolating effects of social distancing measures have been felt acutely by the entire population and may be especially profound in older demographics, relatively little scientific evidence on the subject is currently available. A recent study published in the Pan American Journal of Public Health aimed to provide further information on the implications of social distancing measures on patient mental health.

Coping with Coronavirus Isolation

A team of researchers aimed to examine the impact of isolation and social distancing among adults aged 60 and above during the COVID-19 outbreak in the United States. To conduct this analysis, the study’s authors asked convenience sampling respondents to complete a web-administered survey exploring the effects of social distancing on mental health factors, including loneliness, stress, and behavioral changes. In total, data from 833 responses from participants aged 60 and above were included in the sample.

Effects of Social Distancing on Older Patients

Of the total survey respondents, 36% reported being stressed while nearly 43% reported feelings of loneliness. Approximately one-third of participants reported feelings of increased loneliness during the social distancing period specifically. Respondents also reported engaging in more solitary activities and fewer in-person activities, using email and text messages more than usual, and spending more time using technology than before.

The study’s authors noted significant differences between younger patients aged 60-70 and those above the age of 71; changes in physical activity, drinking, recreational drug use, and sleeping pattern were found to differ by age. Participants over the age of 71 showed more resiliency with 74% experiencing little to no stress, according to the authors.

“That’s where older adults have a strength,” lead researcher and clinical associate professor at the University of Georgia’s Institute of Gerontology Kerstin Emerson told HealthDay. “They have life experience and coping mechanisms that we don’t often give them credit for, but that’s part of their wisdom. We can really turn to older adults as examples of how to manage and live through bad periods of history.”

Furthermore, two-thirds of survey respondents reported using more social media than they would before the pandemic began revealing that older adults are actively engaging in other forms of social connection and becoming increasingly comfortable online. However, for some older individuals remote connections may be more difficult to achieve due to a lack of internet or smart device access; Emerson noted that her team’s results don’t reflect the most vulnerable populations socially isolated in rural areas or those without sufficient economic resources.

As social distancing regulations and isolation measures persist across the globe, it is important to consider the effects of these strategies on mental health – especially among older adults in the United States. The latest findings indicate the potential adverse psychiatric effects associated with continued shelter-in-place practices and highlight the need for increased mental health screening among vulnerable populations at this time.