Sex Differences in Influenza: The Challenge Study Experience.

Area of Science:

• Immunology
• Infectious Diseases
• Sex Differences in Health

Background:

• Emerging evidence suggests adult females face poorer influenza outcomes compared to males.
• Prospective human studies are needed to confirm these observations.

Purpose of the Study:

• To prospectively investigate sex-based differences in influenza A/H1N1 challenge outcomes.
• To identify predictors of influenza symptoms and viral shedding.

Main Methods:

• 164 healthy volunteers received an influenza A/H1N1 challenge.
• Compared baseline characteristics, hormone levels, hemagglutination inhibition (HAI) titers, and neuraminidase inhibition (NAI) titers between sexes.
• Utilized regression models to analyze predictors of outcomes.

Main Results:

• Females reported more symptoms (P=.003) and a higher symptom count (P=.011) than males.
• NAI titers were higher in males at 4 and 8 weeks post-challenge.
• Prechallenge NAI titers, not HAI titers or sex hormones, predicted symptom and shedding outcomes.

Conclusions:

• Females were more likely to be symptomatic after influenza challenge.
• NAI titers emerged as a key predictor of influenza outcomes, potentially explaining sex-based differences.