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. 2022 Sep 11;11:40. doi: 10.1186/s40035-022-00316-y

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — SARS-CoV-2 invades the CNS through the olfactory nerve. Once SARS-CoV-2 enters the nasal cavity, it contacts with olfactory epithelial cells, which express ACE2 and NRP-1 receptors at high levels, rendering the epithelium vulnerable to SARS-CoV-2 infection. The infected olfactory epithelial cells potentially transmit the virus to the surrounding cells, such as horizontal basal cells as well as immature and mature olfactory neurons. The infected horizontal basal cells also mature into olfactory sensory neurons. These neuronal cells extend to the apex, contact the air, and form small nerve bundles at the base before passing through the ethmoid plate and forming the olfactory nerve. Infected olfactory neurons are connected to neurons in the olfactory bulb through synapses, which allows the virus to spread from the olfactory nerve to the olfactory bulb via retrograde transport along axons. The olfactory bulb makes many connections throughout the brain, allowing the virus to spread quickly to other structures in the brain