Sex and gender combine with other societal constructs such as race and age to determine how a person will respond to a disease like COVID-19. Detailed data collection on patients’ sex and gender will be necessary to appropriately tailor medical interventions and understand the underlying mechanisms of disease and this pandemic.
Dr. Sabra Klein, a professor of Molecular Microbiology and Immunology at the Bloomberg School of Public Health, studies the biological role sex plays in the human body’s response to infection and development of disease. Sex and gender are critically underdiscussed in research. Biological differences between males and females and social differences between men and women need to be considered, including in statistical models.
A sex difference is based in biology, referring to whether you have two X chromosomes (female) or an X and a Y chromosome (male), and which sex steroids (testosterone, estrogen, and progesterone) your reproductive tissues secrete. Almost every cell in our bodies possesses receptors for sex steroids. Whether we're talking about the heart, brain, bone, or the immune system, there are sex differences in healthy functioning as well as the development and outcomes of disease.
Gender differences are operationally defined as differences between those who identify as men and those who identify as women based on societal or cultural norms. That includes where we work, who we take care of, and how socially acceptable it is or is not to express feelings of pain, admit you need to go to a hospital, or admit you need to go to a doctor. Both gender and sex are critical factors when discussing health and disease.
One of the first observations from reports out of Wuhan was that men were significantly more likely to be hospitalized and to die from the disease. As COVID-19 spread, this trend was confirmed in several European countries and the United States. We saw this as well in our Johns Hopkins Health System, using our JH-CROWN data. There are considerably more males than females who've been hospitalized and have died from COVID-19, especially prior to large-scale rollout of the vaccines.
There are some, but not many, studies that indicate males may not be as good at controlling the virus replication, with males having more virus than females. Another immunological aspect that we've contributed to the research on is showing that many inflammatory markers are up-regulated in males as compared with females during the acute phase of COVID-19. Biological females seem to be regulating their immune responses better than males.
With all these established sex and gender differences, I want to start seeing greater consideration, especially in the context of vaccines, about whether a one-size-fits-all approach really works equally well in all people. I want to see consideration of whether individuals are male or female entering into the discussion. We have different doses and formulations of the flu vaccine depending on your age, but across diverse ages our data suggests that the decay of immunity seems to occur more quickly in men than women. I hope that we get to a point where sex is considered in these decisions, and we will need more detailed data to make these discussions productive.
In Caucasians, younger women are more likely to be vaccine-hesitant, whereas African-American men are a bit more hesitant about vaccines and the medical community than African-American women. However, you can only see this in studies that have enough data to disaggregate both by gender as well as by race.
There's also the intersection with age. You're more likely to see people report vaccine hesitancy at younger ages, maybe at ages where they feel that they are not vulnerable to negative or adverse outcomes from an infectious disease, but as people get older you start to see vaccine hesitancy wane. Then, when you start to look at individuals 65 years and older, some of these gender-associated differences disappear because at older ages maybe it's socially acceptable for everybody to admit vulnerability and try to reduce susceptibility to infectious diseases.
I'm very interested in transgender individuals, and this is where biology can intersect with social science. They create an interesting opportunity to try to understand biologically what's driving a sex difference in a response because you can have individuals who may have a sex chromosome complement, but a hormonal environment that is divergent from their sex chromosome complement. You can have an XY individual who is now getting exposed to SARS-CoV-2 vaccination in a hormonal environment that is rich in estrogen and progesterone.
Data from these individuals could be a boon to research, but I haven’t noticed that discussion in many fields apart from the cardiovascular literature. Most recent transgender-focused research investigates trust of the medical community, the impact of the pandemic on sex confirming surgery and receipt of hormones, and what constitutes essential/non-essential surgeries.
The American Heart Association's Go Red for Women initiative came about to let biological females know they may present heart attack symptoms differently, and that is true for transgender individuals as well. Data indicates that people’s hormone levels at the time they start experiencing disease are huge predictors of whether they're going to show a male-typic or a female-typic pattern. If we don’t have accurate data on the intricacies of a patient’s biological sex, then they may not receive the right medical information.
For more discussion of sex and gender data with Dr. Klein, please look for an upcoming Pandemic Data Outlook blog.