SARS-CoV-2: Olfaction, Brain Infection, and the Urgent Need for Clinical Samples Allowing Earlier Virus Detection

Rafal Butowt, Katarzyna Bilinska, Rafal Butowt, Katarzyna Bilinska

Abstract

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.

Keywords: ACE2 expression; COVID-19; SARS-CoV-2; TMPRSS2 expression; olfactory epithelium; respiratory epithelium; viral brain infection.

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Diagram of human nasal cavity with respiratory and olfactory epithelium areas indicated in blue and yellow, respectively.
Figure 2
Figure 2
Basic organization of the olfactory epithelium (OE). Olfactory neurons continuously regenerate through human life and therefore are at different stages of differentiation. Some non-neuronal cells are shown, e.g., progenitors, sustentacular cells, and olfactory ensheathing cells.

References

    1. Ou X.; Liu Y.; Lei X.; Li P.; Mi D.; Ren L. (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 11, 1620.10.1038/s41467-020-15562-9.
    1. Hoffmann M.; Kleine-Weber H.; Schroeder S.; Kruger N.; Herrler T.; Erichsen S.; Schiergens E. S.; Herrler G.; Wu N.-H.; Nitsche A.; Muller M. A.; Drosten C.; Pohlmann S. (2020) SARS-CoV-2 cell entry depends on ACE2 and TRMPSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 1–10. 10.1016/j.cell.2020.02.052.
    1. Ruiz Garcia S.; Deprez M.; Lebrigand K.; Cavard A.; Paquet A.; Arguel M.-J.; Zaragosi L.-E. (2019) Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures. Development 146, dev.177428.10.1242/dev.177428.
    1. Olender T.; Keydar I.; Pinto J. M.; Tatarskyy P.; Alkelai A.; Chien M.-S.; Fishilevich S.; Restrepo D.; Matsunami H.; Gilad Y.; Lancet D. (2016) The human olfactory transcriptome. BMC Genomics 17, 619.10.1186/s12864-016-2960-3.
    1. Kangeswaran N.; Demond M.; Nagel M. (2015) Deep sequencing of the murine olfactory receptor transcriptome. PLoS One 10 (1), e0113170.10.1371/journal.pone.0113170.
    1. Saraiva L. R.; Ibarra-Soria X.; Khan M.; Omura M.; Scialdone A.; Mombaerts P.; Marioni J. C.; Logan D. W. (2015) Hierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq. Sci. Rep. 5, 18178.10.1038/srep18178.
    1. Netland J.; Meyerholz D. K.; Moore S.; Cassell M.; Perlman S. (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol 82 (5), 7264–75. 10.1128/JVI.00737-08.
    1. Harberts E.; Yao K.; Wohler J. E.; Maric D.; Ohayon J.; Henkin R.; Jacobson S. (2011) Human herpesvirus-6 entry into CNS through the olfactory pathway. Proc. Natl. Acad. Sci. U. S. A. 108 (33), 13734.10.1073/pnas.1105143108.
    1. Baig A. M.; Khaleeq A.; Ali U.; Syeda H. (2020) Evidence of the COVID-19 virus targeting the CNS: host-virus interactions and proposed neurotropic mechanisms. ACS Chem. Neurosci. 11, 995.10.1021/acschemneuro.0c00122.
    1. Sepahi A.; Kraus A.; Casadei E.; Johnston C. A.; Galindo-Villegas J.; Kelly C.; Garcia-Moreno D.; Munoz P.; Mulero V.; Huertas M.; Salinas I. (2019) Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner. Proc. Natl. Acad. Sci. U. S. A. 116 (25), 12428–36. 10.1073/pnas.1900083116.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere