The immune-endocrine interplay in sex differential responses to viral infection and COVID-19.

Men are at higher risk for developing severe COVID-19 than women, while women are at higher risk for developing post-acute sequelae of COVID-19 (PASC). This highlights the impact of sex differences on immune responses and clinical outcomes of acute COVID-19 or PASC. A dynamic immune-endocrine interface plays an important role in the development of effective immune responses impacting the control of viral infections. In this opinion article we discuss mechanisms underlying the transcriptional and epigenetic regulation of immune responses by sex hormones during viral infections. We propose that disruption of this delicate immune-endocrine interplay can result in worsened outcomes of viral disease. We also posit that insights into these immune mechanisms can propel the development of novel immunomodulatory interventions that leverage immune-endocrine pathways to treat viral infections.