Sex Differences in Influenza: The Challenge Study Experience

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.