Department of Medicine, Discipline of Nephrology, Federal University of Sao Paulo, São Paulo, Brazil.
Research Center of the Hospital Sacré-Coeur, CIUSSS Nord-de-l'Île-de-Montréal, Montréal, Canada.
Clin Sci (Lond). 2021 Aug 13;135(15):1805-1824. doi: 10.1042/CS20210284.
In times of coronavirus disease 2019 (COVID-19), the impact of severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme (ACE) 2 (ACE2), the main receptor for SARS-CoV-2, in human placentas indicates that this organ can be vulnerable for viral infection during pregnancy. However, for this to happen, additional molecular processes are critical to allow viral entry in cells, its replication and disease manifestation, particularly in the placenta and/or feto-maternal circulation. Beyond the risk of vertical transmission, COVID-19 is also proposed to deplete ACE2 protein and its biological actions in the placenta. It is postulated that such effects may impair essential processes during placentation and maternal hemodynamic adaptations in COVID-19 pregnancy, features also observed in several disorders of pregnancy. This review gathers information indicating risks and protective features related to ACE2 changes in COVID-19 pregnancies. First, we describe the mechanisms of SARS-CoV-2 infection having ACE2 as a main entry door and current evidence of viral infection in the placenta. Further, we discuss the central role of ACE2 in physiological systems such as the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), both active during placentation and hemodynamic adaptations of pregnancy. Significant knowledge gaps are also identified and should be urgently filled to better understand the fate of ACE2 in COVID-19 pregnancies and the potential associated risks. Emerging knowledge will be able to improve the early stratification of high-risk pregnancies with COVID-19 exposure as well as to guide better management and follow-up of these mothers and their children.
在 2019 年冠状病毒病（COVID-19）时期，严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）感染对妊娠的影响尚不清楚。血管紧张素转换酶（ACE）2（SARS-CoV-2 的主要受体）在人胎盘的存在表明，该器官在妊娠期间可能容易受到病毒感染。然而，要做到这一点，还需要其他分子过程来允许病毒进入细胞、复制和表现疾病，特别是在胎盘和/或胎-母循环中。除了垂直传播的风险外，COVID-19 还被提议耗尽胎盘中的 ACE2 蛋白及其生物学作用。据推测，这些影响可能会损害 COVID-19 妊娠中胎盘发生和母体血液动力学适应的重要过程，这在几种妊娠疾病中也有观察到。这篇综述收集了表明 COVID-19 妊娠中 ACE2 变化相关风险和保护特征的信息。首先，我们描述了 SARS-CoV-2 感染以 ACE2 为主要进入门户的机制和目前在胎盘感染中的证据。此外，我们讨论了 ACE2 在生理系统中的核心作用，如肾素-血管紧张素系统（RAS）和激肽释放酶-激肽系统（KKS），它们在胎盘发生和妊娠血液动力学适应期间都很活跃。还确定了显著的知识空白，应紧急填补这些空白，以更好地了解 ACE2 在 COVID-19 妊娠中的命运以及潜在的相关风险。新出现的知识将能够改善对 COVID-19 暴露的高危妊娠的早期分层，以及更好地管理和随访这些母亲及其子女。
