Estrogens, progesterone and allopregnanolone may protect against Covid-19 during pregnancy
The finding that in Covid-19-positive asymptomatic pregnant women, symptoms became severe immediately following parturition, suggests that reproductive steroids provide protection. It is indeed remarkable that symptoms in these patients appeared at the same time that levels of estradiol, progesterone and allopregnanolone declined postpartum. In addition to the role of immunoregulatory role of estradiol, progesterone, allopregnanolone regulates inflammatory processes by reshaping the competence of immune cells and inhibiting pro-inflammatory marks suggesting a protective role during late pregnancy in SARS-CoV-2-positive women. These observations collectively suggest that reproductive steroids may offer a treatment opportunity to improve COVID-19 symptoms in men and in post-menopausal women.
In spite of the lack of substantive data showing pregnant women are resilient to the acquisition and/or severe symptoms of COVID-19 compared with women similar in age and co-morbidities, the finding that in COVID-19-positive asymptomatic pregnant women symptoms became severe immediately following parturition, suggests that reproductive steroids may be beneficial. However, in addition to pregnane steroid hormones, other hormones, including human chorionic gonadotropin (hCG), placental growth factor (PlGF), and prolactin as well as proteins produced by the placenta (e.g., leptin) have well recognized roles in immunomodulation during pregnancy and could be also involved in the worsening of COVID-19 in the postpartum period.
It is also intriguing that levels of testosterone have been implicated with immunoregulatory roles and in the context of COVID-19, high prevalence in old versus young male patients has been hypothesized to relate to lower testosterone levels in older subjects (40). Of note, not only testosterone can be aromatized to estradiol but the 5α−reduced testosterone metabolite, 3α-diol shows a strong estrogenic activity by binding at ERs.
Estrogens, progesterone and its metabolites are involved in multiple pharmacological effects ranging from improvement of mood disorders to analgesic properties. The anti-inflammatory action and the role in reshaping competence and increasing number of immune cells raise the hypothesis that estradiol, progesterone and allopregnanolone may alleviate COVID-19 symptoms during pregnancy.