Are COVID vaccine side effects worse for some people? It can depend on your sex

Side effects after COVID-19 vaccination are expected, normal and a telltale sign your body is developing the immunity it needs to fend off serious coronavirus illness.

But at least one group of Americans is more likely to experience such reactions.

A Centers for Disease Control and Prevention report published last month found that among the first roughly 13.8 million doses of the Pfizer or Moderna COVID-19 vaccine administered to Americans, only about 7,000 people reported “adverse events” — with most classified as non-serious.

Interestingly, about 5,500 of those reports (79%) occurred in women — in this case, meaning those assigned female at birth — even though they received only 61% of the doses, the report shows.

In a separate CDC study posted in JAMA, researchers learned all of the 19 cases of severe allergic reaction to the Moderna vaccine were in women. The same group experienced 44 of the 47 severe allergic reactions to the Pfizer shot.

So, what’s behind the sex discrepancy when it comes vaccine side effects?

A lot of it has to do with biological differences between males and females — including hormones and genes to the microorganisms that call human bodies home — that may impact responses to the vaccine, as well as some social and cultural distinctions.

But historical data shows the disproportionate COVID-19 vaccine side effects based on sex is nothing to lose sleep over.

“I am not at all surprised,” Dr. Sabra Klein, a microbiologist and immunologist at the Johns Hopkins Bloomberg School of Public Health, told the New York Times. “This sex difference is completely consistent with past reports of other vaccines.”

Studies have shown it’s common for women to experience worse side effects after the influenza, pneumococcal, shingles, tetanus and whooping cough vaccines, according to a 2015 review of research on the topic, which Klein co-authored.

On the other hand, Dr. Thomas Moore, a professor emeritus at the Boston University School of Medicine, was perplexed over the sex disparities.

“One of the most striking things in the table is that the vast majority of cases of anaphylaxis occurred in women… I am aware that, in general, anaphylaxis is more common in women, but not to this extent,” Moore commented below the CDC study published in JAMA. “Perhaps there is something different about these vaccines or mRNA vaccines in general. Certainly worth watching as our experience with these vaccines evolves.”

After receiving the 2009 H1N1 vaccine, women between the ages of 20 and 59 were four times as likely as men within the same age range to experience allergic reactions, one study revealed. And between 1990 and 2016, women made up 80% of all reported adult anaphylactic reactions following vaccination, mostly with influenza shots.

Data also shows that men are less likely to go to the doctor and report feeling side effects after vaccination, experts say, likely because of gender-related roles in society.

For example, “young men may view attending the general practitioner as wimpish and consequently look down on those who bother the doctor with ‘minor’ symptoms,” a 2001 study found. These social ideas around what it means to be masculine could explain why, in the case of COVID-19 vaccination, more women are reporting worse side effects than men.

Dose size may matter, too

In 1977, the U.S. Food and Drug Administration banned most women of “childbearing potential” from participating in clinical research studies based on the notion that some drugs caused serious birth defects. Years later, the medical community began to realize that womens’ body size, hormonal make-up and body fat distribution can affect how drugs are absorbed in their bodies.

“This could potentially mean that life-saving drugs may not work, may not work as well, or may not work similarly, in women as they do in men,” said The Office on Women’s Health, a part of the U.S. Department of Health and Human Services.

It wasn’t until 1993 when the initial ban was lifted and women were allowed to participate in clinical trials.

Although the COVID-19 vaccines were tested equally among men and women in the lab, different dose sizes were not. This could mean lower doses for women may be just as effective in protecting against COVID-19 but cause fewer side effects, Klein of Johns Hopkins told the Times.

Hormones, chromosomes and microbiomes

Biology is also partly to blame for the difference in how male and female immune systems react to vaccines, scientists say.

Males have one X and one Y sex chromosome, while females have two X’s. The X sex chromosome carries a “large number” of genes related to immune system function, so any damages that may occur to these X chromosomes are more likely to affect immune responses in males, the 2015 review said. This could explain why antibody responses to viruses and vaccines are “consistently higher in females than in males.”

Even women’s microbiome — the army of microorganisms such as bacteria and viruses that live in and on the human body — can “directly influence immune function in a sex-specific manner,” the review said. Bacteria can influence which sex hormones and how many are actively working in the body.

And because hormones affect immune systems, this process can also alter reactions to vaccines.