The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
SARS-CoV-2: Olfaction, Brain Infection, and the Urgent Need for Clinical Samples Allowing Earlier Virus Detection
Open accessAbstract
The novel SARS-CoV-2 virus has very high infectivity, which allows it to spread rapidly around the world. Attempts at slowing the pandemic at this stage depend on the number and quality of diagnostic tests performed. We propose that the olfactory epithelium from the nasal cavity may be a more appropriate tissue for detection of SARS-CoV-2 virus at the earliest stages, prior to onset of symptoms or even in asymptomatic people, as compared to commonly used sputum or nasopharyngeal swabs. Here we emphasize that the nasal cavity olfactory epithelium is the likely site of enhanced binding of SARS-CoV-2. Multiple non-neuronal cell types present in the olfactory epithelium express two host receptors, ACE2 and TMPRSS2 proteases, that facilitate SARS-CoV-2 binding, replication, and accumulation. This may be the underlying mechanism for the recently reported cases of smell dysfunction in patients with COVID-19. Moreover, the possibility of subsequent brain infection should be considered which begins in olfactory neurons. In addition, we discuss the possibility that olfactory receptor neurons may initiate rapid immune responses at early stages of the disease. We emphasize the need to undertake research focused on additional aspects of SARS-CoV-2 actions in the nervous system, especially in the olfactory pathway.
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In the citing paper
“Moreover, reported impaired olfaction could be due to CNS invasion or direct damage of olfactory sensory neurons in the nasal cavity [24].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [24]
In the citing paper
“In fact, SARS-CoV, MERS-CoV, and HCoV-OCR43 were able to invade the murine CNS using the transcribrial route, infecting olfactory sensory neurons of nasal cavity, and passing to other neural cells, indicating that SARS-CoV-2 could use the same mechanism [24, 35–37].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [24]
In the citing paper
“COVID-19 patients are suffering acute cerebrovascular disorder and other correlated neurological symptoms as consequences of stroke or micro-strokes [24].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [24]
In the citing paper
“Klok and colleagues observed disturbing increases in the incidence of thrombotic complications in critically ill intensive care unit patients as high as 31% and recommended pharmacological prophylaxis against thrombosis [24].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [24]
Citations
Cites
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Human herpesvirus-6 entry into the central nervous system through the olfactory pathway
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The human olfactory transcriptome
Olender, T., Keydar, I., Pinto, J. M., Tatarskyy, P., Alkelai, A., Chien, M., Fishilevich, S., Restrepo, D., Matsunami, H., Gilad, Y., et al. (2016) · BMC Genomics · doi:10.1186/s12864-016-2960-3 · Cited by 130
Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner
Sepahi, A., Kraus, A., Casadei, E., Johnston, C. A., Galindo‐Villegas, J., Kelly, C., García‐Moreno, D., Muñoz, P., Mulero, V., Huertas, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900083116 · Cited by 93
Deep Sequencing of the Murine Olfactory Receptor Neuron Transcriptome
Kanageswaran, N., Demond, M., Nagel, M., Schreiner, B. S. P., Baumgart, S., Scholz, P., Altmüller, J., Becker, C., Doerner, J. F., Conrad, H., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0113170 · Cited by 85
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Douaud, G., Lee, S., Alfaro-Almagro, F., Arthofer, C., Wang, C., McCarthy, P., Lange, F., Andersson, J. L. R., Griffanti, L., Duff, E., et al. (2022) · Nature · doi:10.1038/s41586-022-04569-5 · Cited by 1,646
Meinhardt, J., Radke, J., Dittmayer, C., Franz, J., Thomas, C., Mothes, R., Laue, M., Schneider, J., Brünink, S., Greuel, S., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00758-5 · Cited by 1,458
Smell dysfunction: a biomarker for COVID‐19
Moein, S. T., Hashemian, S. M. R., Mansourafshar, B., Khorram‐Tousi, A., Tabarsi, P., & Doty, R. L. (2020) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22587 · Cited by 807
Experimental Transmission Studies of SARS-CoV-2 in Fruit Bats, Ferrets, Pigs and Chickens
Schlottau, K., Rissmann, M., Graaf, A., Schön, J., Sehl‐Ewert, J., Wylezich, C., Höper, D. W., Mettenleiter, T. C., Balkema‐Buschmann, A., Harder, T., et al. (2020) · The Lancet Microbe · doi:10.1016/s2666-5247(20)30089-6 · Cited by 469
Baj, J., Karakuła‐Juchnowicz, H., Teresiński, G., Buszewicz, G., Ciesielka, M., Sitarz, R., Forma, A., Karakuła, K. H., Flieger, W., Portincasa, P., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061753 · Cited by 480
Metadata
- Authors
- Butowt, R., & Bilinska, K.
- Affiliations
- L. Rydygier Collegium Medicum, Nicolaus Copernicus University, Ul. CurieSklodowskiej 9, 85-94 Bydgoszcz, Poland
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-04-13
- Volume
- 11
- Issue
- 9
- Pages
- 1200-1203
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W3015599845
- Cited by
- 346
- References
- 10
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 10 · 2023: 32 · 2022: 56 · 2021: 111 · 2020: 124
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Polish National Science Center (UMO-2013/09/B/NZ3/02359)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- SARS-CoV-2, COVID-19 pandemic, olfactory epithelium, olfactory sensory neurons, virus detection, asymptomatic infection, ACE2, TMPRSS2, olfactory dysfunction, brain infection, olfactory pathway, nasal cavity, diagnostic sampling, immune response
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Brain, Humans, Immunity, Innate, Peptidyl-Dipeptidase A, Mass Screening, Olfactory Mucosa, Pneumonia, Viral, Serine Endopeptidases, Smell, Virus Replication, Olfactory Receptor Neurons, Coronavirus Infections, Respiratory Mucosa, Early Diagnosis, Mice, Pandemics
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