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      Effect of SARS-CoV-2 infection in pregnancy on CD147, ACE2 and HLA-G expression

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          Abstract

          Introduction

          Recent studies reported a differential expression of both ACE2 and CD147 in pregnant women associated to SARS-CoV-2 placental infection. The aim of this study is to further investigate the placental SARS-CoV-2 infection and the potential effect on protein expression (ACE2, CD147, HLA-G and CD56).

          Methods

          The study was on three subgroups: i) 18 subjects positive for SARS-CoV-2 swab at delivery; ii) 9 subjects that had a positive SARS-CoV-2 swab during pregnancy but resulted negative at delivery; iii) 11 control subjects with physiological pregnancy and with no previous or concomitant SARS-CoV-2 swab positivity . None of the subjects were vaccinated for SARS-CoV-2 infection. The placenta samples were analyzed for SARS-CoV-2 NP (Nucleocapsid protein) positivity and the expression of ACE2, CD147, HLA-G and CD56.

          Results

          We observed a higher percentage of SARS-CoV-2 NP positive placenta samples in the group of SARS-CoV-2 PCR positive at delivery in comparison with SARS-CoV-2 PCR negative at delivery. The localization of SARS-CoV-2 NP positivity in placenta samples was mainly in syncytiotrophoblast (ST) of SARS-CoV-2 PCR positive at delivery group and in extra-villous trophoblast (EVT) of SARS-CoV-2 PCR negative at delivery group. CD147, HLA-G positivity was higher in ST of SARS-CoV-2 PCR positive at delivery group, while CD56-expressing immune cells were decreased in comparison with control subjects.

          Discussion

          We confirmed the ability of SARS-CoV-2 to infect placenta tissues. The simultaneous SARS-CoV-2 swab positivity at delivery and the positivity of the placenta tissue for SARS-CoV-2 NP seems to create an environment that modifies the expression of specific molecules, as CD147 and HLA-G. These data suggest a possible impact of SARS-CoV-2 infection during pregnancy, that might be worthy to be monitored also in vaccinated subjects.

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          Most cited references38

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          CD56bright natural killer (NK) cells: an important NK cell subset.

          Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56(bright) CD16(dim/) (-) and CD56(dim) CD16(+), respectively. In this review, we will focus on the CD56(bright) NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56(dim) NK cells. CD56(bright) NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.
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            SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis

            SARS-CoV-2 is the causative agent of COVID-19, so understanding its biology and infection mechanisms is critical to facing this major medical challenge. SARS-CoV-2 is known to use its spike glycoprotein to interact with the cell surface as a first step in the infection process. As for other coronaviruses, it is likely that SARS-CoV-2 next undergoes endocytosis, but whether or not this is required for infectivity, and the precise endocytic mechanism used are unknown. Using purified spike glycoprotein and lentivirus pseudotyped with spike glycoprotein, a common model of SARS-CoV-2 infectivity, we now demonstrate that following engagement with the plasma membrane, SARS-CoV-2 undergoes rapid, clathrin-mediated endocytosis. This suggests that transfer of viral RNA to the cell cytosol occurs from the lumen of the endosomal system. Importantly, we further demonstrate that knockdown of clathrin-heavy chain, which blocks clathrin-mediated endocytosis, reduces viral infectivity. These discoveries reveal that SARS-CoV-2 uses clathrin-mediated endocytosis to gain access into cells and suggests that this process is a key aspect of virus infectivity.
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              Vertical transmission of COVID-19: SARS-CoV-2 RNA on the fetal side of the placenta in pregnancies with COVID-19 positive mothers and neonates at birth

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                Author and article information

                Journal
                Placenta
                Placenta
                Placenta
                Elsevier Ltd.
                0143-4004
                1532-3102
                5 January 2023
                February 2023
                5 January 2023
                : 132
                : 38-43
                Affiliations
                [a ]Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121, Ferrara, Italy
                [b ]Department of Medical Sciences, Obstetric and Gynecological Clinic, University of Ferrara, Via Luigi Borsari, 46, 44121, Ferrara, Italy
                [c ]Medical Department, University Hospital of Ferrara Arcispedale Sant'Anna, Via Aldo Moro, 8 Cona, 44124, Ferrara, Italy
                [d ]Department of Translational Medicine, University of Ferrara, Via Luigi Borsari, 46, 44121, Ferrara, Italy
                [e ]Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia
                [f ]LTTA—Clinical Research Center, University of Ferrara, Via Luigi Borsari, 46 - 44100, 44121, Ferrara, Italy
                Author notes
                []Corresponding author. Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121, Ferrara, Italy.
                [1]

                Equally contributed to the research.

                Article
                S0143-4004(23)00011-5
                10.1016/j.placenta.2023.01.004
                9814282
                74ee8db6-12e2-414b-85ff-21428aba15d0
                © 2023 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 14 June 2022
                : 20 December 2022
                : 4 January 2023
                Categories
                Article

                Obstetrics & Gynecology
                sars-cov-2,placental infection,ace2,cd147,hla-g,sars-cov-2, severe acute respiratory syndrome coronavirus 2,ace-2, angiotensin converting enzyme 2,tmprrs2, transmembrane serine protease 2,covid-19, coronavirus disease 2019,hla, human leukocyte antigen,nk, natural killer,kir, killer-cell immunoglobulin-like receptor,ilt, ig-like transcript

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