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.