Challenge study demonstrates women experience worse flu outcomes
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A challenge study demonstrated that women are more likely than men to be symptomatic and have more symptoms of influenza.
“We were drawn into this topic after Sabra L. Klein, PhD, who is also a co-author on the paper, gave a presentation on sex differences in influenza at NIH. There are data, in both animal and human studies, characterizing differences between the biological sexes in outcomes with influenza disease,” Luca T. Giurgea, MD, a clinical fellow in the Laboratory of Infectious Diseases Clinical Studies Unit at the NIH and National Institute of Allergy and Infectious Diseases, told Healio.
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Giurgea explained that animal studies have shown higher rates of inflammation and more robust immune responses in females, whereas studies in humans have also shown females may have more robust responses to vaccines, at least with respect to hemagglutination inhibition (HAI) titers. Additionally, retrospective studies in humans have shown that reproductive age females have higher rates of influenza and influenza-related hospitalizations, but there may be many contributing factors, including genetic, hormonal, cultural or behavioral, that are “difficult to disentangle,” Giurgea said.
“Our research group has performed numerous influenza challenge studies, providing an opportunity to disentangle at least some of the social determinants of illness from the biological ones,” Giurgea said. “So, we decided to aggregate our data from past studies to see if we also observe differences between sexes.”
Giurgea, Klein and colleagues compiled data from 164 healthy volunteers who underwent influenza A/California/04/2009/H1N1 challenge and compared differences between sexes. According to the study, the researchers compared baseline characteristics, including hormone levels, HAI titers, neuraminidase-inhibition (NAI) titers and outcomes after challenge.
Overall, the study demonstrated that HAI titers were similar between the sexes. However, NAI titers were higher in males than in females at 4 weeks and 8 weeks after challenge. Additionally, the study demonstrated that females were more likely to have symptoms (0.96 vs. 0.80; P = .003) and to have a higher number of symptoms (3 vs. 4; P = .011) than males.
According to the study, modeling showed that baseline NAI titers were predictive of all shedding and symptom outcomes assessed in the study, whereas HAI titers and sex hormone levels were not.
“This study confirms the observation that females have worse clinical outcomes with influenza compared to males,” Giurgea said. “However, this study found this interesting difference in NAI titers, which has not been studied very well. Additional larger studies looking for differences in NAI titers between sexes in more general populations need to be performed.”
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