SARS-CoV-2 ACE-receptor detection in the placenta throughout pregnancy.
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ABSTRACT:
SUBMITTER: Gengler C
PROVIDER: S-EPMC7532787 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
SARS-CoV-2 ACE-receptor detection in the placenta throughout pregnancy.
Gengler Carole C Dubruc Estelle E Favre Guillaume G Greub Gilbert G de Leval Laurence L Baud David D
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 20201003 3
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Project description:ObjectivesPregnant women are at increased risk for severe SARS-CoV-2 infection and adverse neonatal outcome, primarily preterm birth and stillbirth. Our study aimed to investigate to which extent SARS-CoV-2 affects placental tissue and if viral replication within the placenta is evident, thus if there is a correlation between placental damage and adverse pregnancy outcome such as stillbirth.MethodsWe prospectively collected placentas from 61 SARS-CoV-2 infected pregnant women and 10 controls. Histopathological, immunohistochemical, and in situ hybridization studies were performed on all placentas with antibodies for SARS-CoV-2 proteins, ACE2, various immune cells, and inflammatory markers or probes for SARS-CoV-2 genes and an antisense strand.ResultsThe measured scores of SARS-CoV-2 glycoprotein, nucleocapsid, and antisense strand indicating replication correlated with both the severity of maternal symptoms and presence of stillbirth. Specifically, 15/61 placentas exhibited replication, while the three cases with stillbirth had high or maximal replication scores. ACE2-H-score was significantly higher in COVID-19 patients, while the expression of various immune cells did not differ statistically. In multivariate analysis, presence of maternal comorbidities correlated with presence of severe COVID-19 infection.ConclusionWe report evidence of active in vivo SARS-CoV-2 replication in the placenta after maternal infection in pregnancy in a case-control setting in a large population. Intensity of placental viral replication as well as viral levels were higher in women with severe or critical COVID-19 disease, supporting the rationale that severity of maternal SARS-CoV-2 infection could correlate with the severity of placentitis. Replication was maximal in cases of stillbirth, which suggests direct placental involvement in the pathophysiology of this dramatic outcome. Continuing to advocate for preventive measures against COVID-19 during pregnancy, including (re)vaccination, as well as appropriately counseling women with diagnosed infection, are of utter importance.
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Project description:The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood. The intervillous spaces and villi were infiltrated with maternal macrophages and T cells. Transcriptome analysis showed an increased expression of chemokines and pathways associated with viral infection and inflammation. Infection of placental cultures with live SARS-CoV-2 and spike protein-pseudotyped lentivirus showed infection of syncytiotrophoblast and, in rare cases, endothelial cells mediated by ACE2 and Neuropilin-1. Viruses with Alpha, Beta, and Delta variant spikes infected the placental cultures at significantly greater levels.
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Project description:Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of proinflammatory cytokines later during infection.
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Project description:Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer's dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.
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Project description:BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.
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