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

作者：Jenny Meinhardt, Josefine Radke, Carsten Dittmayer, Jonas Franz, Carolina Thomas, Ronja Mothes, Michael M. Laue, Julia A. Schneider, Sebastian Brünink, Selina Greuel, Malte Lehmann, Olga Hassan, Tom Aschman, Elisa Schumann, Robert Lorenz Chua, Christian Conrad, Roland Eils, Werner Stenzel, Marc Windgassen, Larissa Rößler, Hans‐Hilmar Goebel, Hans R. Gelderblom, Hubert Martin, Andreas Nitsche, Walter Schulz‐Schaeffer, Samy Hakroush, Martin Sebastian Winkler, Björn Tampe, Franziska Scheibe, Péter Körtvelyessy, Dirk Reinhold, Britta Siegmund, Anja Andrea Kühl, Sefer Elezkurtaj, David A. Horst, Lars Oesterhelweg, Michael Tsokos, Barbara Ingold‐Heppner, Christine Stadelmann, Christian Drosten, Victor M. Corman, Helena Radbruch, Frank L. Heppner · 发表于：Nature Neuroscience · 年份：2020 · DOI：10.1038/s41593-020-00758-5 · 被引用次数：1512 · 研究领域：Olfactory and Sensory Function Studies、Long-Term Effects of COVID-19、COVID-19 Clinical Research Studies

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.