Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients

Mona Khan, Marnick Clijsters, Sumin Choi, Wout Backaert, Michiel Claerhout, Floor Couvreur, Laure Van Breda, Florence Bourgeois, Kato Speleman, Sam Klein, Johan Van Laethem, Gill Verstappen, Ayse Sumeyra Dereli, Seung-Jun Yoo, Hai Zhou, Thuc Nguyen Dan Do, Dirk Jochmans, Lies Laenen, Yves Debaveye, Paul De MunterJan Gunst, Mark Jorissen, Katrien Lagrou, Philippe Meersseman, Johan Neyts, Dietmar Rudolf Thal, Vedat Topsakal, Christophe Vandenbriele, Joost Wauters, Peter Mombaerts, Laura Van Gerven

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5 Citaten (Scopus)
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Samenvatting

Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.

Originele taal-2English
Pagina's (van-tot)3919-3935.e6
Aantal pagina's17
TijdschriftNeuron
Volume110
Nummer van het tijdschrift23
Vroegere onlinedatum10 nov 2022
DOI's
StatusPublished - 7 dec 2022

Bibliografische nota

Funding Information:
We thank the nurses, doctors, and paramedical staff for their support and cooperation; Piet Maes and Björn Rötter for help with variant determination; Arthur Goby, Peter Leemans, Ling Li, Florian Lindenblatt, and Edisa Turkovic for technical support; Patrick Meeze for drawings; and Thomas Boehm and Simon Feys for comments on a draft. T.N.D.D. received a fellowship from EU Horizon 2020 grant OrganoVIR “Organoids for Virus Research - An innovative training - ITN programme.” C.V. and L.V.G. were supported by FWO Senior Clinical Investigator Fellowships 1803923N and 18B2222N , respectively. J.N. was supported by Covid-19-Fund KU Leuven /UZ Leuven and the COVID-19 call of FWO ( G0G4820N ). D.R.T. received support from FWO ( G0F8516N , G065721N ), Stichting Alzheimer Onderzoek (SAO-FRA Belgium, 2020/017 ), and KU Leuven Internal Funding ( C14/17/107 ; C14/22/132 ). P. Mombaerts received financial support from the Max Planck Society .

Publisher Copyright:
© 2022 The Author(s)

Copyright:
Copyright 2023 Elsevier B.V., All rights reserved.

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