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SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: clinical implications

L. Vitale-Cross, I Szalayova, A Scoggins, M. Palkovits, View ORCID ProfileE Mezey
doi: https://doi.org/10.1101/2021.12.30.474580
L. Vitale-Cross
1Adult Stem Cell Section, NIDCR, NIH, 30 Convent Drive, Bethesda, Md 20892
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I Szalayova
1Adult Stem Cell Section, NIDCR, NIH, 30 Convent Drive, Bethesda, Md 20892
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A Scoggins
1Adult Stem Cell Section, NIDCR, NIH, 30 Convent Drive, Bethesda, Md 20892
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M. Palkovits
1Adult Stem Cell Section, NIDCR, NIH, 30 Convent Drive, Bethesda, Md 20892
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E Mezey
1Adult Stem Cell Section, NIDCR, NIH, 30 Convent Drive, Bethesda, Md 20892
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  • ORCID record for E Mezey
  • For correspondence: mezeye@mail.nih.gov
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Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infections result in the temporary loss of smell and taste (anosmia and dysgeusia) in about one third of confirmed cases. Several investigators have reported that the viral spike protein receptor is present in olfactory neurons. However, no study has been published to date showing the presence of viral entry sites angiotensin-converting enzyme 2 (ACE2), neuropilin1 (NRP1), and TMPRSS2, the serine protease necessary for priming the viral proteins, in human nerves that are responsible for taste sensation (cranial nerves: VII, IX and X). We used immunocytochemistry to examine three postmortem donor samples of the IXth (glossopharyngeal) and Xth (vagal) cranial nerves where they leave/join the medulla from three donors to confirm the presence of ACE2, NRP1 and TMPRSS2. Two samples were paraffin embedded; one was a frozen sample. In addition to staining sections from the latter, we isolated RNA from it, made cDNA, and performed PCR to confirm the presence of the mRNAs that encode the proteins visualized. All three of the proteins required for SARS-CoV-2 infections appear to be present in the human IXth and Xth nerves near the medulla. Direct infection of these nerves by the COVID-19 virus is likely to cause the loss of taste experienced by many patients. In addition, potential viral spread through these nerves into the adjacent brainstem respiratory centers might also aggravate the respiratory problems patients are experiencing.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵2 Shared senior authorship

  • Added more recent literature to discussion; expanded Fig.6

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted January 25, 2022.
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SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: clinical implications
L. Vitale-Cross, I Szalayova, A Scoggins, M. Palkovits, E Mezey
bioRxiv 2021.12.30.474580; doi: https://doi.org/10.1101/2021.12.30.474580
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SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: clinical implications
L. Vitale-Cross, I Szalayova, A Scoggins, M. Palkovits, E Mezey
bioRxiv 2021.12.30.474580; doi: https://doi.org/10.1101/2021.12.30.474580

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