Role of hormones in the pregnancy and sex-specific outcomes to infections with respiratory viruses.

Pregnant women infected with pathogenic respiratory viruses, such as influenza A viruses (IAV) and coronaviruses, are at higher risk for mortality, hospitalization, preterm birth, and stillbirth. Several factors are likely to contribute to the susceptibility of pregnant individuals to severe lung disease including changes in pulmonary physiology, immune defenses, and effector functions of some immune cells. Pregnancy is also a physiologic state characterized by higher levels of multiple hormones that may impact the effector functions of immune cells, such as progesterone, estrogen, human chorionic gonadotropin, prolactin, and relaxin. Each of these hormones acts to support a tolerogenic immune state of pregnancy, which helps prevent fetal rejection, but may also contribute to an impaired antiviral response. In this review, we address the unique role of adaptive and innate immune cells in the control of pathogenic respiratory viruses and how pregnancy and specific hormones can impact their effector actions. We highlight viruses with sex-specific differences in infection outcomes and why pregnancy hormones may contribute to fetal protection but aid the virus at the expense of the mother's health.