Sex Differences in Influenza: The Challenge Study Experience.

Document Type


Publication Date


Publication Title

The Journal of infectious diseases


washington; seattle; isb


BACKGROUND: Preclinical animal studies and retrospective human studies suggest that adult females have worse outcomes from influenza than males. Prospective studies in humans are missing.

METHODS: Data from 164 healthy volunteers who underwent Influenza A/California/04/2009/H1N1 challenge were compiled to compare differences between sexes. Baseline characteristics, including hormone levels, hemagglutination-inhibition (HAI) titers, neuraminidase-inhibition titers (NAI), and outcomes after challenge were compared. Linear and logistic regression models were built to determine significant predictor variables with respect to outcomes of interest.

RESULTS: Hemagglutination-inhibition (HAI) titers were similar between the sexes, but neuraminidase-inhibition titers (NAI) were higher in males than females at 4-weeks and 8-weeks post-challenge. Females were more likely to have symptoms (mean 0.96 vs 0.80, p=.003) and to have a higher number of symptoms (median 3 vs 4, p=.011) than males. Linear and logistic regression models showed that pre-challenge NAI titers, but not HAI titers or sex hormone levels, were predictive of all shedding and symptom outcomes of interest.

CONCLUSIONS: Females in our cohorts were more likely to be symptomatic and to have a higher number of symptoms than males. NAI titers predicted all outcomes of interest and may explain differential outcomes between the sexes.


Infectious Diseases


Institute for Systems Biology