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  1. Article ; Online: Hofbauer Cells and COVID-19 in Pregnancy.

    Schwartz, David A / Baldewijns, Marcella / Benachi, Alexandra / Bugatti, Mattia / Bulfamante, Gaetano / Cheng, Ke / Collins, Rebecca R J / Debelenko, Larisa / De Luca, Danièle / Facchetti, Fabio / Fitzgerald, Brendan / Levitan, Daniel / Linn, Rebecca L / Marcelis, Lukas / Morotti, Denise / Morotti, Raffaella / Patanè, Luisa / Prevot, Sophie / Pulinx, Bianca /
    Saad, Ali G / Schoenmakers, Sam / Strybol, David / Thomas, Kristen / Tosi, Delfina / Toto, Valentina / van der Meeren, Lotte E / Verdijk, Robert M / Vivanti, Alexandre J / Zaigham, Mehreen

    Archives of pathology & laboratory medicine

    2021  Volume 145, Issue 11, Page(s) 1328–1340

    Abstract: ... of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells ... whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and ... other villous stromal cells in infected placentas of liveborn and stillborn infants.: Design.—: Case-based ...

    Abstract Context.—: SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown.
    Objective.—: To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants.
    Design.—: Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells.
    Results.—: Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2.
    Conclusions.—: SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.
    MeSH term(s) Adult ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/transmission ; COVID-19/virology ; Cell Proliferation ; Endothelium/pathology ; Endothelium/virology ; Female ; Humans ; Hyperplasia/pathology ; Hyperplasia/virology ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Macrophages/pathology ; Macrophages/physiology ; Macrophages/virology ; Male ; Placenta/pathology ; Placenta/virology ; Pregnancy ; Pregnancy Complications, Infectious/immunology ; Pregnancy Complications, Infectious/pathology ; Pregnancy Complications, Infectious/virology ; Retrospective Studies ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Stillbirth ; Trophoblasts/pathology ; Trophoblasts/virology
    Language English
    Publishing date 2021-07-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 194119-7
    ISSN 1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
    ISSN (online) 1543-2165
    ISSN 0363-0153 ; 0096-8528 ; 0003-9985
    DOI 10.5858/arpa.2021-0296-SA
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts.

    Enninga, Elizabeth Ann L / Quach, Huy Quang / Jang, Jin Sung / de Araujo Correia, Maria Cristina Miranda / Fedyshyn, Yaroslav / Fedyshyn, Bohdana / Lemens, Maureen / Littlefield, Dawn / Behl, Supriya / Sintim-Aboagye, Elise / Mejia Plazas, Maria C / Cardenas, Maria C / Chakraborty, Shree / Yamaoka, Satoko / Ebihara, Hideki / Pandey, Akhilesh / Li, Hu / Badley, Andrew D / Johnson, Erica L /
    Sun, Jie / Norgan, Andrew P / Theiler, Regan N / Chakraborty, Rana

    PLoS pathogens

    2024  Volume 20, Issue 2, Page(s) e1011990

    Abstract: Background: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations ... CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways ... Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 ...

    Abstract Background: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus.
    Methods: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid.
    Results: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells.
    Conclusions: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.
    MeSH term(s) Pregnancy ; Female ; Humans ; Placenta ; COVID-19/genetics ; COVID-19/metabolism ; SARS-CoV-2/genetics ; Trophoblasts/metabolism ; Transcriptome ; RNA, Messenger/metabolism
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2024-02-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011990
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19.

    Morotti, Denise / Cadamuro, Massimiliano / Rigoli, Elena / Sonzogni, Aurelio / Gianatti, Andrea / Parolin, Cristina / Patanè, Luisa / Schwartz, David A

    Pathogens (Basel, Switzerland)

    2021  Volume 10, Issue 4

    Abstract: ... syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells ... of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown ... 2 via the transplacental route to determine whether Hofbauer cells have evidence of infection ...

    Abstract A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.
    Language English
    Publishing date 2021-04-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens10040479
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19

    Denise Morotti / Massimiliano Cadamuro / Elena Rigoli / Aurelio Sonzogni / Andrea Gianatti / Cristina Parolin / Luisa Patanè / David A. Schwartz

    Pathogens, Vol 10, Iss 479, p

    2021  Volume 479

    Abstract: ... syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells ... of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown ... 2 via the transplacental route to determine whether Hofbauer cells have evidence of infection ...

    Abstract A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.
    Keywords Hofbauer cell ; SARS-CoV-2 ; placenta ; COVID-19 ; fetal infection ; coronavirus ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19

    Morotti, Denise / Cadamuro, Massimiliano / Rigoli, Elena / Sonzogni, Aurelio / Gianatti, Andrea / Parolin, Cristina / Patanè, Luisa / Schwartz, David A

    Pathogens. 2021 Apr. 15, v. 10, no. 4

    2021  

    Abstract: ... syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells ... of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown ... 2 via the transplacental route to determine whether Hofbauer cells have evidence of infection ...

    Abstract A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.
    Keywords COVID-19 infection ; Human immunodeficiency virus ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; Zika virus ; antibodies ; antigens ; basement membrane ; fetus ; immunohistochemistry ; macrophages ; necrosis ; neonates ; nucleocapsid proteins ; pregnant women ; transplacental transmission ; trophoblast ; viruses
    Language English
    Dates of publication 2021-0415
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens10040479
    Database NAL-Catalogue (AGRICOLA)

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