Influenza Challenge Study Explores Sex Differences

NIAID Now | May 29, 2021

Studies in animal models and observational clinical studies provide evidence that males and females have differing outcomes to influenza infection and vaccination.  Due to the number of variables related to sex and gender differences associated with disease outcomes, it is difficult to define which are critical using retrospective data.  As such, influenza challenge studies offer a controlled environment to better understand the mechanisms underlying these differing outcomes between the sexes.  

To elucidate key differences in influenza disease outcomes and underlying immune responses between males and females, NIH researchers analyzed data from four influenza challenge studies involving healthy volunteers at baseline, followed by 4 and 8 weeks post-challenge. Females in these studies experienced worse outcomes to influenza challenge compared to males.  However, although baseline hormone levels were not predictive of differential outcomes between the sexes, neuraminidase inhibition (NAI) titers at 4 and 8 weeks post-challenge were found to be predictive of outcomes of interest, with higher levels in male subjects. This finding suggests a potential mechanism for the differential disease outcomes experienced between the sexes in these studies. 

This study supported earlier findings that females experience different influenza outcomes than males and provided insight into the mechanisms that may contribute to this disparity. Larger studies including additional immune response variables are needed to better understand the observed differences in NAI titers and their contribution to the variation in disease consequences between the sexes.

Giurgea et al. Sex Differences in Influenza: The Challenge Study Experience. The Journal of Infectious Diseases, 2021, jiab422.

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