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

Abstract

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.

Mendelian Randomization Study: Investigating the Causal Impact of Covid-19 on Adverse Pregnancy Outcomes

“…Such an imbalance might amplify pathological vasoconstriction, brosis, in ammation, and thrombosis, all of which are detrimental to the pregnancy process. [25] The infection may also interfere with the normal functioning of endometrial cells, contributing to reproductive failure such as miscarriage.…”

“…This is partly due to the differing levels of binding a nity that ACE2 receptors have for the S-protein of the virus. [25] Additionally, earlier research has indicated that in ammasomes play a role in the pathophysiology of the infection, suggesting that they could serve as indicators of COVID-19 infection.…”

SARS-CoV-2 Infection in the Second Trimester of Pregnancy: A Case Report of Fetal Intraventricular Hemorrhage After Critical COVID-19 Infection and a Brief Review of the Literature

“…ACE2 is located weakly only at the stromal side of the syncytiotrophoblast of the trophoblast villous, whereas it is quite indetectable on the maternal endothelial side that hosts few TMPRSS2 receptors [ 10 ], partially explaining the extremely rare vertical transmission [ 16 , 23 ]. The main biological role of ACE is to convert angiotensin I (Ang I) to angiotensin II (Ang II), which binds AT1 receptors [ 24 ]. At the same time, ACE2 produces angiotensin 1-7 (Ang 1-7) that inhibits AT II via the activation of the anti-inflammatory MAS receptors [ 24 ].…”

“…The main biological role of ACE is to convert angiotensin I (Ang I) to angiotensin II (Ang II), which binds AT1 receptors [ 24 ]. At the same time, ACE2 produces angiotensin 1-7 (Ang 1-7) that inhibits AT II via the activation of the anti-inflammatory MAS receptors [ 24 ]. Ang 1-7 determines vasodilating, anti-inflammatory, anti-fibrotic, and anti-thrombotic effects [ 24 ].…”

Desfechos clínicos e perinatais de gestantes com e sem Covid-19 não vacinadas submetidas a parto cesariano: estudo de coorte retrospectivo

“…Um fator primordial na evolução da doença é o estado de imunidade, tendo os indivíduos com imunidade mais comprometida uma maior chance de doença severa, com maior possibilidade de agravamento e necessidade de suporte intensivo. Esses são notadamente os idosos e as gestantes com comorbidades como hipertensão, diabetes e obesidade (Figueiro-Filho, 2021;Wang et al, 2022).…”