COVID-19 Vaccine Side Effects Are Stronger in Women

"Is there a culture of men not wanting to speak up when they have symptoms? That may be part of it,” says Anne Liu, an allergist, immunologist and infectious disease specialist at Stanford University School of Medicine.

But Liu, Donnelly and other experts say biological differences also play a role.

Women have stronger immune responses

Historically, women have a stronger immune response to vaccines than men, and experts say that's the most likely reason for their more intense side effects.

"It means that women's immune systems are responding to the vaccine, and that is a positive thing, so you know it's working,” says Rosemary Morgan, a scientist who studies gender differences at Johns Hopkins Bloomberg School of Public Health.

In studies and research, women and girls produce more infection-fighting antibodies than men when they get vaccinations for influenza, yellow fever, rabies, hepatitis A and B, and MMR (measles, mumps and rubella), Morgan says.

The more robust female immune response is also why women are generally better at fighting off infections such as sepsis, pneumonia and, now, COVID-19. Studies show that men who get COVID-19 are almost three times as likely to require intensive care as women who are infected, and they're also more likely to die.

On the other hand, women are twice as likely as men to have autoimmune diseases such as lupus, rheumatoid arthritis and psoriasis — another consequence of their strong immune response. In those disorders, the body's immune system mistakenly attacks the body and causes inflammation.

Donnelly says the same phenomenon could also explain why women are more likely to identify as “long-haulers” — COVID-19 survivors who have symptoms that last for months after they are no longer infected with the coronavirus. Many doctors believe the condition isn't caused by the virus itself, Donnelly says, but “from the immune system going into overdrive and fighting even after the virus has been cleared.”

Hormones, genes may play a role

Experts aren't sure exactly why men and women have such different immune responses, but hormones probably play a role. Studies have linked high amounts of testosterone to a weaker immune response, while estrogen and progesterone seem to boost the body's defenses.

A small study published in March 2021 in the journal Chest found that giving hospitalized male COVID-19 patients the female hormone progesterone improved clinical outcomes.

Scientists have also identified several genes related to immunity that reside on the X chromosome, points out Panagis Galiatsatos, M.D., a physician in the Division of Pulmonary and Critical Care Medicine at Johns Hopkins Medicine. Men have just one X chromosome, while women have two.

If one of your immunity genes is defective, you'll have a weakened response when a virus invades, Galiatsatos says. “But women have a reserve, an extra X that allows them to compensate,” he says.

Are doses sized for men?

Gender bias in drug development and the size of vaccine doses could also play a role. Women have historically been excluded from many clinical trials and research studies, Morgan says. Even now, sex-segregated data is rarely reported when vaccines and medications are tested.

"Could women be receiving more dose than they need?” Morgan asks. “They are smaller, they have less muscle, they metabolize things differently.”

It's also possible a lower dose would be just as effective in women and cause fewer side effects, she says.

Fortunately, most side effects from the COVID-19 vaccine — which include headache, fever and chills — are mild and go away within a few days.

Donnelly says she felt tired and achy the day after her first dose of COVID-19 vaccine, while her husband felt good enough to “landscape our entire yard.” But she recommends focusing on the positive: “I remember thinking, Great, this is my body kicking into gear, so I'll be protected in the future."

Michelle Crouch is a contributing writer who has covered health and personal finance for some of the nation's top consumer publications. Her work has appeared in Reader's Digest, Real Simple, Prevention, The Washington Post and The New York Times.