Role of hormones in the pregnancy and sex‐specific outcomes to infections with respiratory viruses*

Abstract

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.

Local immune recognition of trophoblast in early human pregnancy: controversies and questions

“…Antibody responses to trophoblast antigens shed into the circulation in mice and humans are inhibited by sialoglycoproteins characteristic of trophoblast 180 . Pregnancy is associated with an increased maternal susceptibility to viral infections, although the clinical course of respiratory infections is also affected by pregnancy-related changes to lung physiology 181 , 182 . Changes in the severity of autoimmune symptoms occur during pregnancy, commonly in patients with multiple sclerosis or rheumatoid arthritis, which further supports the idea that systemic changes in the immune response occur — to self-antigens as well as to fetal and pathogen antigens 183 , 184 .…”

“…Pregnancy is associated with an increased maternal susceptibility to viral infections, although the clinical course of respiratory infections is also affected by pregnancy-related changes to lung physiology 181 , 182 .…”

Introduction to the immunology of pregnancy

“…While there is an active and very specific mechanism preventing a maternal immune response against paternal antigens, the trophoblast and the maternal immune system have evolved and established a cooperative status, helping each other for the success of the pregnancy. The placenta, through cytokines and hormones secreted by trophoblast cells, educate uterine maternal immune cells, 31 and determines the immunological environment at the maternal/fetal interface, as well as at the maternal systemic immune system 32–35 . Interestingly, many of the maternal immunological changes that take place during pregnancy remain after the delivery of the fetus, suggesting a long term effect of the pregnancy on the maternal immune system 36 and another major difference from the original conceptualization of pregnancy as a host/graft immunological process.…”

“…Although the maternal immune system and the placenta is well prepared to contain and control the majority of viral infections, as exemplified by COVID‐19 pandemic, the impact on the immunological response of the normal development of the fetus is unknown. Dr. Adams Waldorf's group 35 and Dr. Menon 21 discuss the impact of pregnancy on viral responses and the Fetal Inflammatory Syndrome. Similarly, Dr. Ding and colleagues 6 discuss novel mechanism of protection by the placenta against viral infections while preventing an exacerbated inflammatory response.…”

“…Signals form the embryo will inhibit the expression of chemokines and will shift the phenotype of local macrophages leading to tolerance, placentation and fetal growth by trophoblast educate uterine maternal immune cells, 31 and determines the immunological environment at the maternal/fetal interface, as well as at the maternal systemic immune system. [32][33][34][35] Interestingly, many of the maternal immunological changes that take place during pregnancy remain after the delivery of the fetus, suggesting a long term effect of the pregnancy on the maternal immune system 36 and another major difference from the original conceptualization of pregnancy as a host/graft immunological process. The second explanation proposed by Medawar was a generalized maternal immune suppression, similar to what is induced in transplant patients.…”