Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19
Jenny MeinhardtDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyJosefine RadkeBerlin Institute of Health (BIH), Berlin, GermanyCarsten DittmayerDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyJonas FranzCampus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, GermanyCarolina ThomasInstitute of Neuropathology, University Medical Center, Göttingen, GermanyRonja MothesDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyMichael LaueCentre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Berlin, GermanyJulia SchneiderInstitute 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, GermanySebastian BrüninkInstitute 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, GermanySelina GreuelInstitute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyMalte LehmannDivision 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, GermanyOlga HassanDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyTom AschmanDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyElisa SchumannDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyRobert Lorenz ChuaCenter for Digital Health, Berlin Institute of Health (BIH) and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyChristian ConradCenter for Digital Health, Berlin Institute of Health (BIH) and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyRoland EilsCenter for Digital Health, Berlin Institute of Health (BIH) and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyWerner StenzelDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyMarc WindgassenInstitute 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, GermanyLarissa RößlerInstitute 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, GermanyHans‐Hilmar GoebelDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyHans R. GelderblomCentre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Berlin, GermanyHubert MartinDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyAndreas NitscheCentre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Berlin, GermanyWalter Schulz‐SchaefferInstitute of Neuropathology, University of the Saarland, Homburg, GermanySamy HakroushInstitute of Pathology, University Medical Center Göttingen, Göttingen, GermanyMartin Sebastian WinklerDepartment of Anaesthesiology and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, GermanyBjörn TampeDepartment of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, GermanyFranziska ScheibeCluster of Excellence, NeuroCure, Berlin, GermanyPéter KörtvelyessyDepartment of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyDirk ReinholdInstitute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyBritta SiegmundDivision 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, GermanyAnja A. KühlCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, and iPATH.Berlin, Berlin, GermanySefer ElezkurtajCharité - Universitätsmedizin BerlinDavid HorstInstitute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyLars OesterhelwegInstitute 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, GermanyMichael TsokosInstitute 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, GermanyBarbara Ingold‐HeppnerInstitute of Pathology, DRK Kliniken Berlin, Berlin, GermanyChristine StadelmannInstitute of Neuropathology, University Medical Center, Göttingen, GermanyChristian DrostenInstitute 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, GermanyVictor M. CormanInstitute 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, GermanyHelena RadbruchDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyFrank L. HeppnerBerlin Institute of Health (BIH), Berlin, Germany. [email protected]
2020en
ABI
Аннотация
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. The authors demonstrate the presence of SARS-CoV-2 in the nasopharynx and brain, suggesting that the virus is present in the CNS and may enter through the olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue.
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