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The New York Times

Women Report Worse Side Effects After a COVID Vaccine

The morning Shelly Kendeffy received her second dose of the Modern COVID-19 vaccine, she felt fine. In the afternoon, he noticed pain in his arm and body, and at night, he felt like the flu. “My teeth were chattering, but I was sweating, like soaked, but frozen,” said Kendeffy, 44, a medical technician at State College, Pennsylvania. The next day, he went to work and surveyed his colleagues, eight men and seven women, about their experiences with vaccines. Six of the women had body aches, chills, and fatigue. The only woman who had no flu symptoms was up most of the night vomiting. Sign up for The Morning newsletter from the New York Times. The eight men gave drastically different reports. One had mild arm pain, headache, and body aches. Two described mild fatigue and some pain. One had a headache. And four had no symptoms. “I work with some very tough women,” Kendeffy said. But “clearly, women suffer a number of side effects.” She felt better after 24 hours and is delighted that she received the vaccine. “I wouldn’t change anything, because it sure outperforms the alternative,” he said. “But he didn’t know what to expect either.” The differences Kendeffy observed among his co-workers are manifesting across the country. In a study published last month, researchers from the Centers for Disease Control and Prevention analyzed 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 the vaccines had been administered to women. Almost all rare anaphylactic reactions to COVID-19 vaccines have also occurred among women. The CDC researchers reported that the 19 people who had experienced such a reaction to the Moderna vaccine were women, and that the women were 44 of the 47 who had had anaphylactic reactions to the Pfizer vaccine. “I’m not surprised at all,” said Sabra Klein, a microbiologist and immunologist at the Johns Hopkins Bloomberg School of Public Health. “This sex difference is completely consistent with previous reports of other vaccines.” In a 2013 study, scientists from the CDC and other institutions found that four times more women than men between the ages of 20 and 59 reported allergic reactions after receiving the 2009 pandemic flu vaccine, although more men than women received those. vaccines. Another study found that between 1990 and 2016, women accounted for 80% of all adult anaphylactic reactions to vaccines. In general, women “have more reactions to a variety of vaccines,” said Julianne Gee, medical officer for the CDC’s Office of Immunization Safety. That includes flu vaccines given to adults, as well as some given in childhood, such as the hepatitis B and measles, mumps, and rubella (MMR) vaccines. However, the news is not all bad for women. Side effects are usually mild and short-lived. And these physical reactions are a sign that a vaccine is working, that “it is generating a very robust immune response and, as a result, it will probably be protected,” Klein said. But why do these sex differences occur? Part of the answer could be behavioral. Women may be more likely than men to report side effects even when their symptoms are the same, said Rosemary Morgan, an international health researcher at the Johns Hopkins Bloomberg School of Public Health. There’s no specific vaccine research to support this claim, but men are less likely than women to see a doctor when they’re sick, so they’re also less likely to report side effects, he said. Still, there is no question that biology plays an important role. “The female immune response is different, in many ways, from the male immune response,” said Eleanor Fish, an immunologist at the University of Toronto. Research has shown that women and girls produce more, sometimes twice as many, infection-fighting antibodies in response to influenza, MMR, yellow fever, rabies, and hepatitis A vaccines compared to their male counterparts, and B. The stronger responses of immune fighters called T cells are often increased as well, Gee noted. These differences are usually strongest among younger adults, “suggesting a biological effect, possibly associated with reproductive hormones,” he said. Sex hormones, including estrogen, progesterone, and testosterone, can bind to the surface of immune cells and influence their function. Exposure to estrogen causes immune cells to produce more antibodies in response to the flu vaccine, for example. And testosterone, Klein said, “is wonderfully immunosuppressive.” The flu vaccine tends to be less protective in men with a lot of testosterone compared to men with fewer sex hormones. Among other things, testosterone suppresses the body’s production of immune chemicals known as cytokines. Genetic differences between men and women can also influence immunity. Many genes related to the immune system are found 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 on and the other was inactive. But research now shows that 15% of genes escape this inactivation and are more expressed in women. These strong immune responses help explain why 80% of autoimmune diseases affect women. “Women have greater immunity, either against ourselves, against the antigen in a vaccine or against a virus,” said Klein. The size of the vaccine dose can also be important. Studies have shown that women absorb and metabolize drugs differently than men, so they often need lower doses to get the same effect. But until the 1990s, clinical trials of drugs and vaccines largely excluded women. “The drug dosages that are recommended are historically based on clinical trials involving male participants,” Morgan said. Today’s clinical trials include women. But in the trials of the new COVID vaccines, the side effects were not separated or analyzed enough by sex, Klein said. And they didn’t test whether lower doses could be just as effective for women but cause fewer side effects. Until they do, Klein said, healthcare providers should talk to women about the side effects of vaccines so they don’t scare them. “I think it is valuable to prepare women so that they can experience more adverse reactions,” she said. “That is normal and probably reflects how your immune system is working.” This article originally appeared in The New York Times. © 2021 The New York Times Company

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