Why COVID-19 Affects Men and Women Differently

Why COVID-19 Affects Men and Women Differently

Months into the COVID-19 pandemic, there is still so much we don’t know about the novel coronavirus and how exactly it affects the body. What we do know is that some groups of people suffer more-severe symptoms and die at higher rates than others. Men, the elderly, people of color, and those with preexisting medical conditions are among these groups.

JoAnn Manson, MD, DrPH, is the chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor at both Harvard Medical School and the Harvard T.H. Chan School of Public Health. She recently coauthored an article in Annals of Internal Medicine on what we have to learn about sex and gender differences in health during this pandemic. While we don’t have all the answers at this time, Manson tells us that we do know where to start: with the specific biology and behaviors that determine our health at any other time.

A Q&A with JoAnn Manson, MD, DrPH

Why do we study sex and gender differences in health?

Sex- and gender-informed medicine is tremendously important for providing optimal health care and improving population health. With our current focus on precision medicine, sex- and gender-informed medicine is fundamental to that goal. It may be helpful to clarify what we mean by the terms. When we refer to sex differences, we’re talking about the biological and physiological traits that characterize males and females. With gender, we’re talking about a continuum of sociocultural roles and behaviors associated with men, women, and gender-spectrum diversity. There are many sex-based differences in health, from risk factors to the reliability of diagnostic testing to responses to therapeutics and treatments. Gender-based roles and behaviors also affect most aspects of our health, including our interactions with the health care system.

What are the main things to consider when we talk about health in terms of sex and gender?

Biological differences

There are sex- and gender-based biological differences in many aspects of health. We know that there are tremendous differences in the prevalence of disease by sex. Certain conditions are more common in women, such as osteoporosis, multiple sclerosis, autoimmune disorders, and depression. There are other conditions that are more common in men, such as coronary heart disease, Parkinson’s disease, and ALS (amyotrophic lateral sclerosis). So we already know about differences in disease prevalence, but it’s just as important to keep in mind that there are sex- and gender-based differences in how diseases manifest themselves. Think about the symptoms of heart disease, as an example. There is a great deal of overlap in symptoms, but there are also distinct differences: Heart attacks are generally known to cause crushing chest pain, but that’s a symptom more prevalent in men. Women are more likely than men to have symptoms such as nausea, shortness of breath, or pain in the jaw or neck.

We consider sex differences when we develop and prescribe medications because of how sex hormones interact with medications and because of differences in body size and the volume of distribution, metabolism, and excretion of drugs. Many drugs have different dose recommendations in men and women because of these differences. (For example, women are more sensitive to the sleeping medication Zolpidem [Ambien] and to anticlotting medications.) So there are differences not only in disease prevalence but also in symptom presentation and response to therapeutics.

“It’s also more common for men than women to have a sense of invincibility: ‘This will not affect me, so I don’t need to worry about it.’”

This is also relevant to infectious disease because there’s a biological basis for sex differences in the immune response. We know that some of the genes that determine our immune response are on the X chromosome. Hormonal differences can also account for the fact that women tend to have more robust immune responses than men. In addition, we know that those at the highest risk of poor clinical outcomes are older adults and those who have comorbidities, such as diabetes, obesity, hypertension, and coronary heart disease. And there’s a higher prevalence of coronary heart disease, emphysema, and some of these other risk factors in men than in women.

It’s also important to think about sex and gender when we talk about the influence of health conditions on emotional well-being. Women are known to be more susceptible to stress-related disorders, such as anxiety, depression, and post-traumatic stress disorders. In terms of the COVID pandemic, although men are more likely to die from COVID, women may be more susceptible to the long-term mental and emotional repercussions of prolonged isolation and the stress and fear associated with a pandemic virus.

Sociocultural and behavioral differences

There are many behavioral factors that could relate to the risk of contracting an infection as well as the risk of poor outcomes related to that infection. And of the behavioral factors that influence health as a whole, many of them are affected by sociocultural factors, including our perceived gender roles in society.

Some examples: the likelihood an individual will seek medical attention for their symptoms when they get sick, how vigilant they are about their medical appointments and taking their prescribed medications, and even handwashing and other preventive behaviors for transmissible disease. These are important for overall health as well as the risk of COVID-19. Some studies suggest gender differences favoring women in many of these areas. It’s also more common for men than women to have a sense of invincibility: “This will not affect me, so I don’t need to worry about it.”

Men may also be more likely to smoke—and in some countries there are enormous differences in smoking between men and women. Smoking is a risk factor for many health conditions, including severe COVID illness.

However, women have been particularly adversely affected by job loss and financial strains related to COVID, given that women are more likely to be employed in the service industries that have been most heavily impacted by the pandemic.

What have researchers observed about how COVID-19 affects men and women differently?

Men and women in most countries are at a similar risk of contracting the COVID infection. However, men are at higher risk of dying from it and are more likely to become critically ill and have poor clinical outcomes. For example, in Italy, a report from April showed a sex difference in which approximately 70 percent of the COVID deaths occurred in men. In the United States, the proportion of COVID-related deaths that are in men has been running closer to 55 to 60 percent. Other countries that have looked at this, including China and South Korea, have also seen sex differences.

Why do you think COVID-19 affects men and women differently?

The first component of the immune response to think about is the immediate fending off of the virus when it has contact with the body. Women do tend to have more robust innate immunity and a stronger immune response. Women also tend to have a greater response to vaccinations than men. We also know that sex hormones—including estrogen, progesterone, testosterone—play a role in the immune response.

We also have to think about the inflammatory response that occurs in the lungs and the cytokine storm1 that often leads to respiratory distress and the need for mechanical ventilation. That process can also be influenced by sex hormones. Estrogen and progesterone may play a role in keeping the immune response from going into overdrive and producing that cytokine storm. This may help in tamping down and modulating the inflammatory response. These hormonal differences, therefore, may be contributing to the sex and gender differences in COVID outcomes.

There are now randomized trials being conducted to leverage this information about hormonal differences in the immune response. For example, there is research looking at the effects of transdermal estradiol and progesterone in improving proving immune response and tamping down the pro-inflammatory response and cytokine storm that can increase the risk of poor clinical outcomes.

Thus, sex- and gender-related factors are critically important in our general health, as well as in our risks of developing or dying from COVID-19. We believe that sex- and gender-related factors need to be incorporated into research, clinical practice, and public health measures. This is likely to lead to more effective prevention and treatment strategies, as well as improved health for the entire population.

JoAnn Manson, MD, DrPH, is a physician epidemiologist and endocrinologist. Manson is the chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School, and a professor of epidemiology at the Harvard T.H. Chan School of Public Health. Her research focus is on the role of hormonal and lifestyle factors in health, especially in the prevention of chronic diseases. She has received numerous honors and was elected to the Institute of Medicine (National Academy of Medicine) in 2011.

This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.

1Cytokines are a group of proteins involved in cell signaling and modulating the immune system. When the body releases large quantities of cytokines, the immune system begins to attack the body’s own cells, not just the infection it’s targeting. This is called a “cytokine storm.” Cytokine storms seem to be responsible for at least some of the more severe symptoms of COVID-19.