The New York Times
Women report worse side effects after a COVID vaccine
The morning that Shelly Kendeffy received her second dose of the Modern COVID-19 vaccine, she felt good. In the afternoon, she noticed a sore arm and body aches and, at night, she looked like the flu. “My teeth were chattering, but I was sweating – like soaking, but frozen,” said Kendeffy, 44, a medical technician at State College, Pennsylvania. The next day, she went to work and interviewed her colleagues – eight men and seven women – about their experiences with the vaccine. Six of the women had body aches, chills and fatigue. The only woman who had no flu symptoms spent most of the night throwing up. Subscribe to the New York Times newsletter The Morning. The eight men reported dramatically different stories. One had a mild pain in his arm, a headache and body aches. Two described mild fatigue and some pain. One got a headache. And four had no symptoms. “I work with some very tough women,” said Kendeffy. But “clearly, we women suffer from the severity of side effects.” She felt better after 24 hours and is thrilled to have received the vaccine. “I would not change anything, because it is certainly better than the alternative,” she said. “But I also didn’t know what to expect.” The differences that Kendeffy noted between his co-workers are happening across the country. In a study published last month, researchers at the Centers for Disease Control and Prevention analyzed the safety data for the first 13.7 million doses of the COVID-19 vaccine administered to Americans. Among the side effects reported to the agency, 79.1% came from women, although only 61.2% of vaccines have been administered to women. Almost all of the rare anaphylactic reactions to COVID-19 vaccines have also occurred among women. The CDC researchers reported that all 19 individuals who experienced such a reaction to the Modern vaccine were women, and that women were 44 of the 47 who had anaphylactic reactions to the Pfizer vaccine. “I’m not at all surprised,” said Sabra Klein, a microbiologist and immunologist at the Johns Hopkins Bloomberg School of Public Health. “This gender difference is completely consistent with previous reports of other vaccines.” In a 2013 study, scientists at CDC and other institutions found that four times as many women as men between 20 and 59 years old reported allergic reactions after receiving the 2009 pandemic flu vaccine, although more men than women received these vaccines. Another study found that between 1990 and 2016, women were responsible for 80% of all anaphylactic reactions in adults to vaccines. In general, women “have more reactions to a variety of vaccines,” said Julianne Gee, a doctor at the CDC’s Office of Immunization Security. This includes influenza vaccines given to adults, as well as some given in childhood, such as vaccines against hepatitis B and measles, mumps and rubella (MMR). But the news is not all bad for women. Side effects are generally mild and of short duration. And these physical reactions are a sign that the vaccine is working – that “you are building a very robust immune response and are likely to be protected as a result,” said Klein. But why do these sex differences happen? Part of the answer may be behavioral. It is possible that women are more likely than men to report side effects, even when their symptoms are the same, said Rosemary Morgan, international health researcher at the Johns Hopkins Bloomberg School of Public Health. There is no specific vaccine research to support this claim, but men are less likely than women to see a doctor when they are sick, so they are also less likely to report side effects, she said. Still, there is no doubt that biology plays an important role. “The female immune response is distinct in many ways from the male immune response,” said Eleanor Fish, an immunologist at the University of Toronto. Research has shown that, compared to their male counterparts, women and girls produce more – sometimes twice as much – of infection-fighting antibodies in response to vaccines for influenza, MMR, yellow fever, rabies and hepatitis A and B. They often boost stronger responses from immune fighters called T cells as well, noted Gee. These differences are often more pronounced among younger adults, which “suggests a biological effect, possibly associated with reproductive hormones,” she said. Sex hormones, including estrogen, progesterone and testosterone, can bind to the surface of immune cells and influence how they work. Exposure to estrogen causes immune cells to produce more antibodies in response to the flu vaccine, for example. And testosterone, said Klein, “is a kind of wonderful immunosuppressant.” The flu vaccine tends to be less protective in men with a lot of testosterone compared to men with less of the sex hormone. Among other things, testosterone suppresses the production of chemicals in the immune system known as cytokines. Genetic differences between men and women can also influence immunity. Many genes related to the immune system are on the X chromosome, of which women have two copies and men only one. Historically, immunologists believed that only one X chromosome in women was activated and that the other was deactivated. But research now shows that 15% of genes escape this inactivation and are more expressed in women. These robust immune responses help explain why 80% of autoimmune diseases afflict women. “Women have greater immunity, either against ourselves, against a vaccine antigen, or against a virus,” said Klein. The dose size of the vaccine can also be important. Studies have shown that women absorb and metabolize drugs differently than men, often requiring lower doses for the same effect. But until the 1990s, clinical trials of drugs and vaccines largely excluded women. “Recommended drug dosages are historically based on clinical trials involving male participants,” said Morgan. Current clinical trials include women. But in testing for the new COVID vaccines, the side effects were not sufficiently separated and analyzed by sex, Klein said. And they haven’t tested whether lower doses can be as effective for women, but they cause fewer side effects. Until they do, Klein said, health professionals should talk to women about the side effects of the vaccine so they are not afraid of them. “I think it is important to prepare women so that they can experience more adverse reactions,” she said. “This is normal and probably reflects the functioning of their immune system.” This article was originally published in The New York Times. © 2021 The New York Times Company