Women twice as likely as men to report local flu, COVID vaccine side effects, data suggest

Vaccinating a woman

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Women are more than twice as likely as men to report local adverse events (AEs) after influenza or COVID-19 vaccination, with more disruptions in daily life, concludes a study published in Biology of Sex Differences.

Johns Hopkins researchers surveyed healthcare workers (HCWs) recruited from the medical center's mandatory fall flu vaccination campaign from 2019 to 2022 and the fall 2022 bivalent (two-strain) COVID-19 vaccination campaign. Vaccinees enrolled the day of vaccination and completed an AE survey 2 days later.

A total of 300 HCWs were vaccinated against flu (50 women and 50 men per year), with AE data available for 88% of recipients (50.2% women). The average flu-vaccine recipient age was 30.8 years, 60.8% were White, 19.4% were Asian, 13.2% were Hispanic, and 12.9% were Black. 

Of the 212 COVID-19 vaccine recipients, AE data was available for 92% (76.5% women). The average age was 38.4 years, 64.8% were White, 20.9% were Asian, and 8.7% were Black.

No difference in systemic side effects

Among the 265 flu vaccine recipients across the 3 years, 62% reported one or more AEs, with 57% having only local AEs, 21% reporting only systemic AEs, and 21% having both.

Of the 178 flu vaccinees who answered a question about inconvenience, 80% said they experienced no inconvenience, 17% reported mild inconvenience in which they were able to complete 75% to 99% of their daily activities, 2% reported moderate inconvenience in which they could complete 25% to 75%, and 1% said they had severe inconvenience in which they could do 0% to 25%.

In total, 86% of the 196 COVID-19 vaccine recipients reported at least one AE (30% only local, 18% only systemic, and 51% both). Most (53%) reported no inconvenience, 23% reported mild inconvenience, 18% reported moderate inconvenience, and 5% reported severe inconvenience.

"Overall, these data suggest that experiencing mild AEs is common following vaccination, with minimal impairment to daily activities," the researchers wrote.

Women were more likely than men to experience local (injection-site) AEs after vaccination against flu (odds ratio [OR], 2.28) and COVID-19 (OR, 2.57), regardless of race or age. But rates of systemic AEs (ie, malaise, muscle pain, insomnia, headache, fever, chills, and sweating) were similar for men and women after flu (OR, 1.18) or COVID-19 (OR, 0.96) vaccine receipt. Use of hormonal birth control didn't significantly affect AE rates in women of reproductive age.

Considering sex in workplace vaccination policy

Women reported more disruptions in daily life after COVID-19 vaccination than men, with 38.7% of women citing sleep disruptions or changes in daily routine, compared with 31.1% of men. They also said that AEs interfered with their ability to take care of their family and were more likely to use over-the-counter medications (24.% vs 15.6% of men) and to schedule COVID-19 vaccination before their days off from work in anticipation of AEs. 

Further sex- and gender- disaggregated research is needed to build more equitable and effective vaccine strategies with consideration for differences in AEs.

"In response to either infection or vaccination, females have been shown to have greater immune activation, higher production of antibodies, and increased T cell activation, possibly making them more likely to experience AEs compared to males," the study authors wrote, noting that women make up nearly 80% of the healthcare workforce.

Post-vaccination AEs can influence vaccine attitudes and uptake patterns, they said: "In the general population, vaccine hesitancy related to influenza and COVID-19 is higher among women than men, which we and others hypothesize to be due to the increased likelihood of AEs in females than males."

The researchers said the results underscore the need for sex-inclusive policies to inform more effective required occupational vaccination strategies. "Further sex- and gender- disaggregated research is needed to build more equitable and effective vaccine strategies with consideration for differences in AEs," they concluded. "Development of such strategies is not only important for seasonal vaccination planning, but also for planning effective vaccination campaigns for HCWs during pandemics."

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