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

Jenny Meinhardt, J. Radke, C. Dittmayer, J. Franz, C. Thomas, R. Mothes, M. Laue, J. Schneider, S. Brünink, S. Greuel, M. Lehmann, O. Hassan, T. Aschman, E. Schumann, R. L. Chua, C. Conrad, R. Eils, W. Stenzel, M. Windgassen, L. Rößler, Hans-Hilmar Goebel, H. R. Gelderblom, H. Martin, A. Nitsche, W. J. Schulz-Schaeffer, S. Hakroush, M. S. Winkler, B. Tampe, F. Scheibe, P. Körtvélyessy, D. Reinhold, B. Siegmund, A. A. Kühl, S. Elezkurtaj, D. Horst, L. Oesterhelweg, M. Tsokos, B. Ingold-Heppner, C. Stadelmann, C. Drosten, V. M. Corman, H. Radbruch & F. L. Heppner

Nat Neurosci (2020). 

Selezionato dal Lettore: Davide Norata - medico in formazione specialistica presso la Clinica Neurologica di Ancona – Università Politecnica delle Marche

MOTIVATION: this study is the elegant demonstration of the trans-ethmoidal pathway as a pathogenic mechanism in SARS-CoV-2 infection, that seems to be responsible for at least some of the well-documented neurological symptoms in COVID-19.

On the apical side of the olfactory mucosa, the dendrites of OSNs (bipolar olfactory sensory neurons) project into the nasal cavity, while on the basal side the axons of OSNs merge into fila, which protrude through the cribriform plate directly into the olfactory bulb, thereby also having contact with CSF.

The authors analyzed the cellular mucosal–nervous micromilieu as a first site of viral infection and replication, followed by thorough regional mapping of the consecutive olfactory nervous tracts and defined CNS regions, in autopsy material from 33 individuals with COVID-19 examined between March and August of 2020. Clinically documented COVID-19-associated neurological alterations included impaired consciousness (n = 5), intraventricular haemorrhage (n = 2), headache (n = 2) and behavioural changes (n = 2); acute cerebral ischemia was reported for 2 individuals, while neuropathological post-mortem workup revealed acute infarcts in 6 individuals.

The results of the different approaches used to detect SARS-CoV-2, including SARS-CoV S immunostaining, RNA Scope in situ hybridizationfor SARS-CoV-2 RNA (ISH) and ultrastructural analyses to visualize CoV particles at various sites and regions, supported the hypothesis of a site-specific, local CNS infection by SARS-CoV-2.