Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19 - PubMed (original) (raw)

. 2021 Feb;24(2):168-175.

doi: 10.1038/s41593-020-00758-5. Epub 2020 Nov 30.

Josefine Radke # 1 2 3, Carsten Dittmayer # 1, Jonas Franz 4 5 6, Carolina Thomas 4 6, Ronja Mothes 1, Michael Laue 7, Julia Schneider 8, Sebastian Brünink 8, Selina Greuel 9, Malte Lehmann 10, Olga Hassan 1, Tom Aschman 1, Elisa Schumann 1 3, Robert Lorenz Chua 11, Christian Conrad 11, Roland Eils 11 12, Werner Stenzel 1, Marc Windgassen 13, Larissa Rößler 13, Hans-Hilmar Goebel 1, Hans R Gelderblom 7, Hubert Martin 1, Andreas Nitsche 7, Walter J Schulz-Schaeffer 14, Samy Hakroush 15, Martin S Winkler 16, Björn Tampe 17, Franziska Scheibe 18 19, Péter Körtvélyessy 18 20, Dirk Reinhold 21, Britta Siegmund 10, Anja A Kühl 22, Sefer Elezkurtaj 9, David Horst 9, Lars Oesterhelweg 13, Michael Tsokos 13, Barbara Ingold-Heppner 23, Christine Stadelmann 4, Christian Drosten 8, Victor Max Corman 8, Helena Radbruch 1, Frank L Heppner 24 25 26 27

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Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Jenny Meinhardt et al. Nat Neurosci. 2021 Feb.

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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