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Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 134-135

Potential pathophysiological mechanisms underlying the loss of smell and taste symptoms of COVID-19

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy

Date of Submission06-Jul-2020
Date of Decision07-Aug-2020
Date of Acceptance09-Aug-2020
Date of Web Publication11-Feb-2021

Correspondence Address:
Dr. Chidiebere Emmanuel Okechukwu
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njecp.njecp_27_20

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How to cite this article:
Okechukwu CE. Potential pathophysiological mechanisms underlying the loss of smell and taste symptoms of COVID-19. Niger J Exp Clin Biosci 2020;8:134-5

How to cite this URL:
Okechukwu CE. Potential pathophysiological mechanisms underlying the loss of smell and taste symptoms of COVID-19. Niger J Exp Clin Biosci [serial online] 2020 [cited 2022 Jul 1];8:134-5. Available from: https://www.njecbonline.org/text.asp?2020/8/2/134/309167


The aim of writing this letter was to explain the possible pathophysiological mechanisms leading to the loss of smell and taste which is a prevalent symptom in patients with mild-to-moderate forms of coronavirus disease 2019 (COVID-19).[1],[2]

Concerning the pathophysiological mechanisms leading to the loss of smell in COVID-19 patients, it was confirmed that the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which is the causal agent of COVID-19 invade the epithelial cells via binding to the angiotensin-converting enzyme 2 (ACE2) protein on the cell surface.[3] Surprisingly, olfactory receptor cells do not express ACE2, as well as TMPRSS2 gene, which are involved in SARS-CoV-2 invasion, so impairment of the olfactory receptors may be facilitated incidentally by SARS-CoV-2 uptake into other cells responsible for supporting the olfactory receptor cells, such cells are the olfactory unsheathing glial cells which have boundary with the olfactory receptor cell axons and form the olfactory fila.[3] Through these olfactory receptor supporting cells, there is the facilitation of ACE2-self-regulating virus, which is transferred into the olfactory receptor neurons through exosomes.[3] As a result of this development, olfactory receptor neurons may initiate a fast immune response in the olfactory epithelium of the nasal cavity, thus leading to olfactory dysfunction.[3] However, the olfactory neuroepithelium can regenerate if the stem cell layer is not obviously damaged; this regeneration could be associated with the spontaneous improvement in olfactory functioning with time, this can be observed in patients who recovered from COVID-19.[3] Moreover, Brann et al.[4] examined large- and single-cell RNA-Seq datasets to detect cell types in the olfactory epithelium which express molecules that mediate infection by SARS-CoV-2. They found in both mouse and human datasets that olfactory sensory neurons do not express two important genes essential for SARS-CoV-2 entry, which are ACE2 and TMPRSS2, whereas olfactory epithelial auxiliary cells and stem cells express both of these genes, as well as cells in the nasal respiratory epithelium. These discoveries propose possible mechanisms by which SARS-CoV-2 may likely result in olfactory dysfunction such as anosmia.

Regarding the loss of taste associated with COVID-19, the possible mechanisms could also be linked to ACE2 receptor in the oral cavity. SARS-CoV-2 possibly enters into the epithelial cells through binding to the ACE2 receptors; ACE2 receptors are expressed diffusely on the mucous membrane of the entire oral cavity, predominantly on the tongue; and ACE2 plays an important role in regulating taste perception, therefore the alterations of ACE2 receptors in these cells may lead to dysgeusia and other gustatory dysfunction.[5]

In conclusion, the pathophysiological mechanisms underlying the loss of sense of smell and taste in patients with COVID-19, may be associated with the binding of SARS-CoV-2 to ACE2 receptors in cells responsible for supporting the olfactory receptor cells and oral cavity, respectively, because ACE2 receptor plays an important role in chemosensory perception. Rationally, loss of smell and taste should be strongly considered as a symptom of SARS-CoV-2, in the early prognosis of COVID-19. Nevertheless, regarding COVID-19 olfactory dysfunction, the target of SARS-CoV-2 may not be neurons but the supporting nonneuronal cells that express ACE2 receptors such as vascular pericytes of the olfactory epithelium and bulb, thus altering the function of the olfactory neurons. However, these findings seriously call for substantial laboratory investigations, most especially histopathological examinations, analyzing samples of nasal mucosa, nasal tissues, mucous membrane of the entire oral cavity, and salivary mucin obtained from COVID-19 patients and patients that died of COVID-19, possibly to recognize the exact cause of these chemosensory alterations associated with COVID-19.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Vaira LA, Deiana G, Fois AG, Pirina P, Madeddu G, De Vito A, et al. Objective evaluation of anosmia and ageusia in COVID-19 patients: Single-center experience on 72 cases. Head Neck 2020;42:1252-8.  Back to cited text no. 1
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. Eur Arch Otorhinolaryngol 2020;277:2251-61.  Back to cited text no. 2
Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL. Smell dysfunction: A biomarker for COVID-19. Int Forum Allergy Rhinol 2020;10:944-50.  Back to cited text no. 3
Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, et al. Nonneural expression of SARS-ClV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVD-19 patients. Sci Adv 2020;6:eabc5801.  Back to cited text no. 4
Vaira LA, Salzano G, Fois AG, Piombino P, De Riu G. Potential pathogenesis of ageusia and anosmia in COVID-19 patients. Int Forum Allergy Rhinol 2020;10:1103-4.  Back to cited text no. 5


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