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Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.
Meinhardt, Jenny; Radke, Josefine; Dittmayer, Carsten; Franz, Jonas; Thomas, Carolina; Mothes, Ronja; Laue, Michael; Schneider, Julia; Brünink, Sebastian; Greuel, Selina; Lehmann, Malte; Hassan, Olga; Aschman, Tom; Schumann, Elisa; Chua, Robert Lorenz; Conrad, Christian; Eils, Roland; Stenzel, Werner; Windgassen, Marc; Rößler, Larissa; Goebel, Hans-Hilmar; Gelderblom, Hans R; Martin, Hubert; Nitsche, Andreas; Schulz-Schaeffer, Walter J; Hakroush, Samy; Winkler, Martin S; Tampe, Björn; Scheibe, Franziska; Körtvélyessy, Péter; Reinhold, Dirk; Siegmund, Britta; Kühl, Anja A; Elezkurtaj, Sefer; Horst, David; Oesterhelweg, Lars; Tsokos, Michael; Ingold-Heppner, Barbara; Stadelmann, Christine; Drosten, Christian; Corman, Victor Max; Radbruch, Helena; Heppner, Frank L.
  • Meinhardt J; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Radke J; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Dittmayer C; Berlin Institute of Health (BIH), Berlin, Germany.
  • Franz J; German Cancer Consortium (DKTK), Partner Site Berlin, CCCC (Campus Mitte), Berlin, Germany.
  • Thomas C; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Mothes R; Institute of Neuropathology, University Medical Center, Göttingen, Germany.
  • Laue M; Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.
  • Schneider J; Max Planck Institute for Experimental Medicine, Göttingen, Germany.
  • Brünink S; Institute of Neuropathology, University Medical Center, Göttingen, Germany.
  • Greuel S; Max Planck Institute for Experimental Medicine, Göttingen, Germany.
  • Lehmann M; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Hassan O; Centre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Berlin, Germany.
  • Aschman T; Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and German Centre for Infection Research, Berlin, Germany.
  • Schumann E; Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and German Centre for Infection Research, Berlin, Germany.
  • Chua RL; Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Conrad C; Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Eils R; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Stenzel W; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Windgassen M; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Rößler L; German Cancer Consortium (DKTK), Partner Site Berlin, CCCC (Campus Mitte), Berlin, Germany.
  • Goebel HH; Center for Digital Health, Berlin Institute of Health (BIH) and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Gelderblom HR; Center for Digital Health, Berlin Institute of Health (BIH) and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Martin H; Center for Digital Health, Berlin Institute of Health (BIH) and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Nitsche A; Health Data Science Unit, Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
  • Schulz-Schaeffer WJ; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Hakroush S; Institute of Legal Medicine and Forensic Sciences, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Winkler MS; Institute of Legal Medicine and Forensic Sciences, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Tampe B; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Scheibe F; Centre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Berlin, Germany.
  • Körtvélyessy P; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Reinhold D; Centre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Berlin, Germany.
  • Siegmund B; Institute of Neuropathology, University of the Saarland, Homburg, Germany.
  • Kühl AA; Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
  • Elezkurtaj S; Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany.
  • Horst D; Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany.
  • Oesterhelweg L; Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Tsokos M; Cluster of Excellence, NeuroCure, Berlin, Germany.
  • Ingold-Heppner B; Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Stadelmann C; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
  • Drosten C; Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
  • Corman VM; Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Radbruch H; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, and iPATH.Berlin, Berlin, Germany.
  • Heppner FL; Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Nat Neurosci ; 24(2): 168-175, 2021 02.
Article in English | MEDLINE | ID: covidwho-1060446
ABSTRACT
The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Brain / Olfactory Mucosa / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Neurosci Journal subject: Neurology Year: 2021 Document Type: Article Affiliation country: S41593-020-00758-5

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Brain / Olfactory Mucosa / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Neurosci Journal subject: Neurology Year: 2021 Document Type: Article Affiliation country: S41593-020-00758-5