Biological Sex and Pregnancy Affect Influenza Pathogenesis and Vaccination

Area of Science:

• Immunology
• Virology
• Epidemiology

Background:

• Sex and age are critical determinants of influenza A virus (IAV) infection severity and outcomes.
• Young children and older adults are most susceptible to severe seasonal influenza, with males often experiencing worse outcomes.
• Reproductive-age females, particularly during pregnancy, face increased risks from pandemic IAV strains, despite generally mounting stronger vaccine responses.

Purpose of the Study:

• To investigate the differential impact of sex and age on influenza A virus pathogenesis.
• To explore how sex steroid hormones influence immune responses to IAV infection and vaccination.
• To highlight the need for integrating sex and age as biological variables in influenza research.

Main Methods:

• Analysis of epidemiological and clinical data on influenza outcomes across different age groups and sexes.
• Review of small animal models examining sex-based differences in immune responses and tissue repair post-IAV infection.
• Examination of the role of sex steroid hormones in modulating immune responses during IAV infection and vaccination.

Main Results:

• IAV infection outcomes vary significantly between males and females, with age being a major modulating factor.
• Males aged <5 and >65 years are at higher risk for severe seasonal influenza than females.
• Reproductive-age females, especially pregnant individuals, exhibit worse outcomes from pandemic IAV strains, contrasting with their generally robust vaccine responses.

Conclusions:

• Sex and age are crucial biological variables that profoundly affect influenza pathogenesis and outcomes.
• Sex steroid hormones directly modulate immune responses, contributing to sex-specific differences in IAV infection and vaccination.
• Future influenza research must incorporate combined analyses of sex and age to fully understand disease dynamics and develop targeted interventions.