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      Placental Tissue Destruction and Insufficiency from COVID-19 Causes Stillbirth and Neonatal Death from Hypoxic-Ischemic Injury: A Study of 68 Cases with SARS-CoV-2 Placentitis from 12 Countries

      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47
      Archives of Pathology & Laboratory Medicine
      Archives of Pathology and Laboratory Medicine

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          ABSTRACT

          Context.—

          Perinatal death is an increasingly important problem as the COVID-19 pandemic continues, but the mechanism of death has been unclear.

          Objective.—

          To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for SARS-CoV-2.

          Design.—

          Case-based retrospective clinico-pathological analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19.

          Results.—

          All 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis, the three findings constituting SARS-CoV-2 placentitis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25/68) and chronic villitis (32%; 22/68). The majority (19, 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs.

          Conclusions.—

          The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

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          Author and article information

          Journal
          Archives of Pathology & Laboratory Medicine
          Archives of Pathology and Laboratory Medicine
          1543-2165
          0003-9985
          February 10 2022
          February 10 2022
          February 10 2022
          February 10 2022
          Affiliations
          [1 ]Atlanta, Georgia, (Schwartz)
          [2 ]Department of Pathology, Fernandes Figueira Institute, FIOCRUZ - Rio de Janeiro, Brazil (Avvad-Portari)
          [3 ]Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia (Babál)
          [4 ]Department of Pathology, University Hospitals Leuven, Leuven, Belgium (Baldewijns)
          [5 ]Department of Obstetrics and Gynecology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden (Blomberg)
          [6 ]Institut de Pathologie Multisite des Hospices Civils de Lyon, Lyon, France; SOFFOET-Société Française de Foetopathologie, Paris, France (Bouachba)
          [7 ]Pathology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain (Camacho)
          [8 ]Department of Pathology, Hopital Femme-Mère Enfant, Hospices Civils de Lyon, Université Claude Bernard Lyon 1 and SOFFOET-Société Française de Foetopathologie, Paris France (Collardeau-Frachon)
          [9 ]Department of Obstetrics, Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium (Colson)
          [10 ]Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent, Belgium (Dehaene)
          [11 ]Pathology Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Barcelona, Spain (Ferreres)
          [12 ]Department of Pathology, Cork University Hospital, Wilton, Cork, Republic of Ireland (Fitzgerald)
          [13 ]Pathology Department, Hospital Universitari Vall d'Hebron, Department of Morphological Sciences, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (Garrido-Pontnou)
          [14 ]Department of Obstetrics and Gynaecology, Doncaster and Bassetlaw NHS Teaching Hospitals, Women's Hospital, Doncaster, United Kingdom (Gerges)
          [15 ]Division of Perinatal Pathology, Department of Cellular Pathology, Birmingham Women's and Children's Hospital, NHS Foundation Trust, Birmingham, United Kingdom (Hargitai)
          [16 ]Immunobiochemistry Department, National Institute of Perinatology, Mexico City, Mexico (Helguera-Repetto)
          [17 ]Department of Obstetrics and Gynaecology, Halland Hospital, Varberg, Sweden (Holmström)
          [18 ]Department of Physiology and Cellular Development, National Institute of Perinatology “Isidro Espinosa de los Reyes”, Mexico City, Mexico (Irles)
          [19 ]Department of Obstetrics and Gynaecology, Helsingborg Hospital, Department of Clinical Science Helsingborg, Lund University, Lund, Sweden (Leijonhfvud)
          [20 ]Department of Pathological Anatomy, Antwerp University Hospital, Edegem, Belgium (Libbrecht)
          [21 ]Cellular Pathology Department, Birmingham Women's Hospital, Birmingham, United Kingdom (Marton)
          [22 ]Histopathology, Rotunda Hospital, Dublin, Republic of Ireland (McEntagart)
          [23 ]Pathology and Laboratory Medicine, CHRISTUS Hospital St. Elizabeth, 2830 Calder St, Beaumont, Texas (Molina)
          [24 ]Department of Pathology and Pediatrics, Autopsy Service, Yale University School of Medicine, New Haven, Connecticut (Morotti)
          [25 ]Pathology Department, Hospital Clínic, Barcelona, Spain (Nadal)
          [26 ]Department of Basic Clinical Practice, School of Medicine, Universitat de Barcelona, and August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain (Nadal)
          [27 ]Pathology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain (Navarro)
          [28 ]Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden (Nelander)
          [29 ]Department of Pathology and Laboratory Medicine, Burrell College of Osteopathic Medicine, Las Cruces, New Mexico (Oviedo)
          [30 ]Laboratório Ferdinando Costa, São Paulo, Brazil (Otani)
          [31 ]Department of Laboratory Medicine, Division of Pathology, Karolinska Institute and Department of Pathology, Karolinska University Hospital, Stockholm, Sweden (Papadogiannakis)
          [32 ]Department of Pathology, Aalborg University Hospital, Aalborg, Denmark (Petersen)
          [33 ]Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (Roberts)
          [34 ]Pediatric Pathology and Neuropathology, Department of Pathology, University of Miami Miller School of Medicine/Jackson Health System/Holtz Children's Hospital, Miami, Florida (Saad)
          [35 ]Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden; Department of Obstetrics and Gynaecology, Karolinska University Hospital, Solna, Stockholm, Sweden (Sand)
          [36 ]Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands (Schoenmakers)
          [37 ]Department of Pathology, St. Louis University School of Medicine, St. Louis, Missouri (Sehn)
          [38 ]Department of Pathology, CHRISTUS Hospital St. Elizabeth, 2830 Calder St., Beaumont, Texas (Simpson)
          [39 ]Department of Pathology, NYU Langone Health – Main Campus & Bellevue Hospital Center, New York University School of Medicine, New York, New York (Thomas)
          [40 ]Department of Anatomical Pathology, National Institute of Perinatology, Mexico City, Mexico (Valdespino-Vázquez)
          [41 ]Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands (van der Meeren)
          [42 ]Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands (van der Meeren)
          [43 ]Department of Pathology, Ghent University Hospital, Ghent, Belgium (Van Dorpe)
          [44 ]Department of Pathology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands (Verdijk)
          [45 ]Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (Watkins)
          [46 ]Obstetrics & Gynecology, Institution of Clinical Sciences Lund, Lund University, Sweden (Zaigham)
          [47 ]Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö and Lund, Sweden (Zaigham)
          Article
          10.5858/arpa.2022-0029-SA
          35142798
          01902ace-7ee5-4c71-8077-c365f4f3fd5f
          © 2022
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