Women often have different and more pronounced — but typically not serious — reactions to COVID-19 vaccines compared with men, as has been widely reported. But most news stories haven’t explored why this is — and, in fact, there may be many reasons for these differences. In a recent episode of the podcast Track the Vax, a professor at the Johns Hopkins Bloomberg School of Public Health explains what we know, and don’t know, about women’s different reactions to these vaccines.
Sabra Klein, PhD, director of the Center for Women’s Health, Sex, and Gender Research at Johns Hopkins, notes that the different reactions between men and women — to both the virus that causes COVID-19, and the vaccines against it — are due, at least in part, to differences in how men’s and women’s immune systems react. Generally speaking, women tend to mount a more robust immune response to a variety of viruses, as measured by levels of cells and proteins that are released to fight off an infection. For this reason, men are much more likely than women to experience severe COVID-19 — they’re about three times as likely as women to be admitted to an intensive care unit (ICU) for the infection. Men were also shown to be more vulnerable to the virus that caused the 2003 SARS outbreak, and they’re more vulnerable to the viruses that cause hepatitis.
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More robust immune response in women
Part of the reason why women tend to mount a more robust immune response, Klein says, is the simple fact that women have two X chromosomes, while men have one X chromosome and one Y chromosome. Many genes that affect the immune system response are on the X chromosome, — and in theory, a person with two X chromosomes shouldn’t express these genes any more than someone with just one X chromosome, because of what’s known as random X inactivation. This means that if you have two copies of a gene on two X chromosomes, one of the two copies — selected at random — will be inactivated and not expressed by your body. But for unknown reasons, this normal biological process doesn’t take place for about 15% of genes linked to the X chromosome. This applies to certain genes involved in the immune system response, so women tend to have better immune responses.
A more robust immune system response can be a good thing when you’re fighting off a virus, but Klein notes that this characteristic most likely also explains why women are more susceptible than men to many autoimmune diseases, in which the immune system mistakenly attacks the body’s own cells and tissues. In fact, about 80% of people with autoimmune diseases are women. The disparity between men and women is extreme for certain conditions, with women nine times as likely to develop lupus and three times as likely to develop multiple sclerosis (MS).
In the case of COVID-19, Klein says that women’s more robust immune response may explain that while men are more likely to experience a severe infection initially, women are more likely to have lingering symptoms from COVID-19. These ongoing symptoms — such as fatigue, headache and cognitive fog — may be related to the immune system’s activation in ways that harm the body.
And a more robust immune response most likely also explains why women are more likely than men to experience an adverse event after receiving a COVID-19 vaccine, with women making up 77% of those who report them. These events typically aren’t severe or life-threatening, ranging from pain at the injection site to fatigue, headache and fever, and usually clear up within a few days. These symptoms indicate that the body is mounting an immune system response, which may be broader and less targeted against the virus in many women.
But Klein also notes another reason why women may report more adverse vaccine reactions than men — that women in our society tend to be more proactive about their health than men. So even if a woman and a man experience the same reaction to a COVID-19 vaccine, the woman may be more likely to report the adverse reaction.
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