Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility.

Published on Aug 13, 2021in Clinical Science5.223
· DOI :10.1042/CS20210284
Nayara Azinheira Nobrega Cruz (UNIFESP: Federal University of São Paulo), Danielle Stoll1
Estimated H-index: 1
(UNIFESP: Federal University of São Paulo)
+ 1 AuthorsMariane Bertagnolli15
Estimated H-index: 15
(McGill University)
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.
#1Karola S Jering (Brigham and Women's Hospital)H-Index: 4
#2Brian Claggett (Brigham and Women's Hospital)H-Index: 68
Last. Scott D. Solomon (Brigham and Women's Hospital)H-Index: 149
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This cohort study compares the clinical characteristics and outcomes of hospitalized women who gave birth with and without coronavirus disease 2019.
42 CitationsSource
#1Yuyang Lei (Xi'an Jiaotong University)H-Index: 4
#2Jiao Zhang (UCSD: University of California, San Diego)H-Index: 9
Last. John Y.-J. Shyy (UCSD: University of California, San Diego)H-Index: 71
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Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial ...
38 CitationsSource
Importance Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive...
66 CitationsSource
#1Shu-Qin Wei (Centre Hospitalier Universitaire Sainte-Justine)H-Index: 20
#2Marianne Bilodeau-Bertrand (UdeM: Université de Montréal)H-Index: 9
Last. Nathalie Auger (Public Health Agency of Canada)H-Index: 27
view all 4 authors...
Background: The impact of coronavirus disease 2019 (COVID-19) on maternal and newborn health is unclear. We aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and adverse pregnancy outcomes. Methods: We conducted a systematic review and meta-analysis of observational studies with comparison data on SARS-CoV-2 infection and severity of COVID-19 during pregnancy. We searched for eligible studies in MEDLINE, Embase, Clin...
25 CitationsSource
#1Sonam Verma (WashU: Washington University in St. Louis)H-Index: 4
#2Chetanchandra S. Joshi (WashU: Washington University in St. Louis)H-Index: 3
Last. Indira U. Mysorekar (WashU: Washington University in St. Louis)H-Index: 19
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Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears to increase the risk of adverse pregnancy outcomes, such as pre-eclampsia in pregnant women. The mechanism(s) by which this occurs remains unclear. Methods We investigated the pathophysiology of SARS-CoV-2 at maternal-fetal interface in pregnant women who tested positive for the virus using RNA in situ hybridization (viral RNA), immunohistochemistry, and hematoxylin and eosin staining. To investigat...
6 CitationsSource
#1Philip McMillan (National Health Service)H-Index: 1
#2Thomas Dexhiemer (MSU: Michigan State University)
Last. Bruce D. Uhal (MSU: Michigan State University)H-Index: 38
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The COVID-19 pandemic caused by the coronavirus SARS-COV-2 has cost many lives worldwide. In dealing with affected patients, the physician is faced with a very unusual pattern of organ damage that is not easily explained on the basis of prior knowledge of viral-induced pathogenesis. It is established that the main receptor for viral entry into tissues is the protein angiotensin-converting enzyme-2 (“ACE-2”, 1). In a recent publication (2), a theory of autoimmunity against ACE-2, and/or against t...
4 CitationsSource
#1Enrrico Bloise (UFMG: Universidade Federal de Minas Gerais)H-Index: 20
#2Jianhong Zhang (Lunenfeld-Tanenbaum Research Institute)H-Index: 11
Last. Stephen J. Lye (U of T: University of Toronto)H-Index: 76
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BACKGROUND: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 cell entry mediators, angiotensin-converting enzyme 2 and transmembrane protease serine 2, at the human maternal-fetal interface. There is also no information as to whether the expression of these mediators is altered in pregnancies complicated b...
19 CitationsSource
#2Jael Miranda (CINVESTAV)H-Index: 5
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Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand facto...
4 CitationsSource
Background Despite the increasingly recognized impact of novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), on many aspects of health in adults and children, its effects on neonates born to infected mothers remain unclear We conducted this study to investigate the outcomes of neonates born to mothers with COVID-19 Methods We searched the medical databases from inception to March 31, 2020 to perform a systematic review of outcomes ...
15 CitationsSource
#1Ryan ChangH-Index: 1
#2Abrar MamunH-Index: 1
Last. Nhat Tu LeH-Index: 15
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Endothelial cells have emerged as key players in SARS-CoV-2 infection and COVID-19 inflammatory pathologies. Dysfunctional endothelial cells can promote chronic inflammation and disease processes like thrombosis, atherosclerosis, and lung injury. In endothelial cells, mitochondria regulate these inflammatory pathways via redox signaling, which is primarily achieved through mitochondrial reactive oxygen species (mtROS). Excess mtROS causes oxidative stress that can initiate and exacerbate senesce...
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