Highly expressed ACE-2 receptors during pregnancy: A protective factor for SARS-COV-2 infection?

While previous viral pandemics showed that pregnancy was a risk factor for susceptibility and adverse outcomes, current evidence is conflicting whether SARS-CoV-2 infection during pregnancy is more severe than in the general population, with relatively low maternal and fetal/neonatal mortality rates. SARS-CoV-2 is known to enter host cells via the ACE-2 receptors, competitively occupying their binding sites. In theory, viral invasion can lead to a reduction in available ACE-2 receptors and consequently an unbalanced regulation between the ACE-AngII-AT1 axis and the ACE-2-Ang-(1-7)-MAS axis, thus enhancing pathological vasoconstriction, fibrosis, inflammation and thrombotic processes. We hypothesize that the normal pregnant state of highly expressed ACE-2 receptors leads to higher Ang-(1-7) levels and consequently more vasodilation and anti-inflammatory response to SARS-COV-2 infection. We suggest that this up-regulation of ACE-2 receptors in human gestation may actually be clinically protective and propose a potential research line to investigate this hypothesis, which may lead to future novel therapeutics.

COVID-19 during pregnancy: an overview of maternal characteristics, clinical symptoms, maternal and neonatal outcomes of 10,996 cases described in 15 countries.

The objective of this review was to identify the most significant studies reporting on COVID-19 during pregnancy and to provide an overview of SARS-CoV-2 infection in pregnant women and perinatal outcomes. Eligibility criteria included all reports, reviews; case series with more than 100 individuals and that reported at least three of the following: maternal characteristics, maternal COVID-19 clinical presentation, pregnancy outcomes, maternal outcomes and/or neonatal/perinatal outcomes. We included eight studies that met the inclusion criteria, representing 10,966 cases distributed in 15 countries around the world until July 20, 2020. The results of our review demonstrate that the maternal characteristics, clinical symptoms, maternal and neonatal outcomes almost 11,000 cases of COVID-19 and pregnancy described in 15 different countries are not worse or different from the general population. We suggest that pregnant women are not more affected by the respiratory complications of COVID-19, when compared to the outcomes described in the general population. We also suggest that the important gestational shift Th1-Th2 immune response, known as a potential contributor to the severity in cases of viral infections during pregnancy, are counter-regulated by the enhanced-pregnancy-induced ACE2-Ang-(1-7) axis. Moreover, the relatively small number of reported cases during pregnancy does not allow us to affirm that COVID-19 is more aggressive during pregnancy. Conversely, we also suggest, that down-regulation of ACE2 receptors induced by SARS-CoV-2 cell entry might have been detrimental in subjects with pre-existing ACE2 deficiency associated with pregnancy. This association might explain the worse perinatal outcomes described in the literature.