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.