Biological Sex and Pregnancy Affect Influenza Pathogenesis and Vaccination.

Males and females differ in the outcome of influenza A virus (IAV) infections, which depends significantly on age. During seasonal influenza epidemics, young children (< 5 years of age) and aged adults (65+ years of age) are at greatest risk for severe disease, and among these age groups, males tend to suffer a worse outcome from IAV infection than females. Following infection with pandemic strains of IAVs, females of reproductive ages (i.e., 15-49 years of age) experience a worse outcome than their male counterparts. Although females of reproductive ages experience worse outcomes from IAV infection, females typically have greater immune responses to influenza vaccination as compared with males. Among females of reproductive ages, pregnancy is one factor linked to an increased risk of severe outcome of influenza. Small animal models of influenza virus infection and vaccination illustrate that immune responses and repair of damaged tissue following IAV infection also differ between the sexes and impact the outcome of infection. There is growing evidence that sex steroid hormones, including estrogens, progesterone, and testosterone, directly impact immune responses during IAV infection and vaccination. Greater consideration of the combined effects of sex and age as biological variables in epidemiological, clinical, and animal studies of influenza pathogenesis is needed.