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Sex Differences in COVID-19

As the novel coronavirus pandemic continues, doctors are seeing trends among patients suggesting men are higher risk than women for experiencing severe or fatal COVID-19. While the rates of COVID-19 infections tend to be similar in men and women in the U.S. and other countries, men are more likely to have severe disease or to die from COVID-19 than women. In the U.S., about 60 percent of COVID-19-related deaths are in men.

“There’s a signal there that men are more likely than women to become critically ill, require ICU care and have fatal COVID-19,” says JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine and scientific advisor to the Mary Horrigan Connors Center for Women’s Health & Gender Biology at Brigham and Women’s Hospital. “The lung involvement and severity of the disease seem to be greater in men than in women.”

The lung involvement is a defining characteristic of COVID-19. The virus creates a tremendous amount of inflammation in the lungs, making it difficult to breathe. Due to this, people who have underlying lung conditions such as emphysema or asthma, and those with a history of smoking, are at higher risk for developing serious illness with COVID-19. If lung illness is exacerbated, it can lead to pneumonia and respiratory failure.

Chronic health conditions also may play a role in the disparity in COVID-19 risk between men and women. This may be because certain chronic health conditions, some of which are related to smoking, are more common in men. These conditions include chronic obstructive pulmonary disease (COPD), emphysema and cardiovascular disease.

A Biological Difference Serves as a Protective Factor

A possible explanation for the sex difference in fatality rates could be due to a long-recognized difference in the immune systems of men and women. “Women have a more aggressive immune response to exposures, like antigens and microbes, which helps protect them against serious disease related to infection and may also boost the effectiveness of vaccinations,” says Dr. Manson. “However, having a robust immune system that may go into overdrive also sets them up to have a greater risk of autoimmune diseases, like rheumatoid arthritis and lupus, than men.” If you have an inflammatory condition, it’s important to take steps to help reduce stress during COVID-19.

There are two sex chromosomes in humans: X and Y. Each person normally has one pair of sex chromosomes in each cell. Men have one X and one Y chromosome, while women have two X chromosomes. Some of the genes for the immune system reside on the X chromosome. This may equip women to better fight viral infections, like COVID-19.

Sex differences in hormone levels also may contribute to differences in COVID-19 outcomes. Two female hormones, estrogen and progesterone, tend to reduce inflammation, while a male hormone, androgen, may promote it. Reducing inflammation helps the immune system heal and fight infections. Inflammation has been linked to serious complications from COVID-19, including blood clots, heart attacks and strokes. Because male hormones may promote inflammation, this may be another reason why men are more likely to experience severe COVID-19 complications than women.

At Brigham and Women’s Hospital, investigators within the Mary Horrigan Connors Center for Women’s Health & Gender Biology seek to understand why and how symptoms, prevalence and treatment of health conditions can affect men and women differently. A commentary, co-authored by Dr. Manson and published in the Annals of Internal Medicine, calls on other institutions to incorporate sex and gender into their research studies.

In “The Fundamentals of Differences” episode of the “Connors Center Conversations” podcast series, Hadine Joffe, MD, MSc, executive director of the Connors Center and vice chair for Psychiatry Research in the Department of Psychiatry at the Brigham, speaks to the role sex and gender play in COVID-19.

“The Connors Center has a general mission to understand sex and gender differences and to improve healthcare for all and studying these differences during the COVID pandemic is very consistent with the mission,” says Dr. Manson.

She emphasizes the importance of including sex (a biological variable) and gender (socio-culturally constructed roles and behaviors) in research. “They can impact clinical care – allowing for appropriate tailoring of interventions or treatments. Some therapies or treatments are much more effective in one sex compared with the other, including treatments that require modification by dose or duration. It’s really important to understand sex and gender differences for the most informed and optimal care,” says Dr. Manson.

Mental Health Concerns for Women Due to COVID-19

Although women may be experiencing less adverse clinical outcomes from COVID-19, they are still at risk for both physical health complications and mental health conditions.

“For example, the isolation and stress associated with the pandemic may pose a disproportionate burden for women in the long-term, because women tend to experience greater stress and have greater risk for post-traumatic conditions,” says Dr. Manson.

These conditions – post-traumatic stress disorder (PTSD), panic attacks, depression, anxiety and mood changes – can be triggered by isolation and stress. They are more common in women than men. The aftermath of the pandemic, whether a few months or a year later, may lead many women to be at increased risk of having mental health repercussions.

Even now, individuals who have mental health disorders may be experiencing new or worsening symptoms related to the crisis. Regardless of your sex, it’s important to understand how to manage your stress and anxiety about the coronavirus.

Sex Differences and Precision Medicine

Precision medicine is an approach for disease treatment and prevention that considers an individual’s genes, environment and lifestyle. Doctors and researchers can use this information to help predict more accurately which treatment and prevention strategies for a particular disease will work in certain people. It allows providers to help tailor treatments for a patient to optimize their health outcomes.

“I think the bottom line is that there’s a need to collect sex- and gender-specific data on COVID-19 and other health conditions, and to present data separately by these variables. For COVID-19, this will help investigators to understand the basis for differences in clinical outcomes and fatality rates and to gain other insights,” says Dr. Manson. “To have the data stratified by sex and gender will facilitate precision medicine and help with the formulation of strategies and policies to improve health for all.”