Sabra Klein addresses the question: how does biological sex influence influenza infection and vaccination? She explains her findings on inflammation differences between males and females, and how these differences can affect the outcome of disease. Klein also discusses her advocacy for inclusion of biological sex in method reporting as a means to improve scientific rigor.

Host: Julie Wolf

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Julie's biggest takeaways:

• Information from the 1918 influenza pandemic suggested males died at a higher rate than females, which could be due to a gender fator or a biological factor. In 1918, men lived in close quarters of military barracks while women didn't, representing a cultural difference of gender norms (women were exempted from military duty). But males are more susceptible to secondary bacterial infections that often accompany flu, which may represent a biological difference in infection outcome. In Klein's studies, female mice suffer influenza more severely than males. Women who contracted the H1N1 flu epidemic in 2009 were more likely to be hospitalized with severe influenza than men. These data have yet to be aligned and leave many variables yet to explore!

• Influenza infection disrupts the female menstrual cycle, causing lowered estrogen and progesterone levels. Providing exogenous progesterone can dampen inflammation and stimulate repair mechanisms needed to fix the damaged lung tissue. This type of host treatment is less likely to lead to the evolution of resistance than using antiviral compounds.

• Females and males respond differently to vaccination; females mount a higher antibody response and have greater cross-protection than males.

• Many diseases in addition to influenza show these sex-specific differences. The sex differences observed are specific to age; with older age, the differences are lost.

• In several other countries, epidemiological and clinical data are analyzed for differences between sexes. With greater awareness, the United States may incorporate this practice too.

Featured Quotes (in order of appearance):

"Both genes as well as the hormones define the biological construct of sex."

"There's an ample amount of data that suggest men are less likely to wash their hands than women. We all know handwashing is probably one of the best ways to avoid contact with viruses - really anything infectious. We always have to question if we do things that influence our exposure; but in our mice studies, we can control their exposure."

"We really have a love-hate relationship with inflammation. We need it to recognize the presence of the virus, but then we need it to dissipate. Our data suggest hormones are integral to regulating inflammation and the repair following inflammation."

"The immune responses to the influenza vaccine - and this extends to many vaccines - are often higher in females as compared with males. This has been shown in humans as well as animal models."

"I don't know that I think that man flu is real. I think a lot can depend on both your age as well as your vaccine status that can influence whether you're going to land in the hospital with severe influenza. Much like we were talking about with individuals who don't have a vaccine, such as during a pandemic, females may be suffering a bit more, but once vaccinated females seem to do better than males. There are some nuances we shouldn't lose sight of."

Links for this episode

• Sabra Klein website
• Klein speaking on heart disease differences in men and women
• Klein editorial in mBio: Sex reporting in microbiological and immunological research
• Smithsonian exhibit notification
• HOM Tidbit: Smithsonian article: How the horrific 1918 flu spread across America
• HOM Tidbit: Aeon article: Who names diseases?

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