Olfactory and Taste Disorders in Patients with SARS-CoV-2 Infection

Since December 2019, a pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally.[1] [2] A spectrum of disease severity has been reported for the infection, with the main symptoms being fever, fatigue, dry cough, myalgia, and dyspnea.[3]

Previous strains of coronavirus have been demonstrated to invade the central nervous system through the olfactory neuroepithelium and propagate from within the olfactory bulb.[4] Furthermore, nasal epithelial cells display the highest expression of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2, in the respiratory tree.[5]

It has been observed that SARS-CoV-2 does not appear to generate clinically significant nasal congestion or rhinorrhea—that is, a red, runny, stuffy, itchy nose. This observation suggests a neurotropic virus that is site-specific for the olfactory system. Although labeled as a virus that affects the respiratory system, coronaviruses are known to be neurotropic and neuroinvasive.[6] [7] [8] [9]

Olfactory and taste disorders are well known to be related with a wide range of viral infections.[10] [11] In a mice model, SARS-CoV has demonstrated a transneural penetration through the olfactory bulb.[12] Moreover, angiotensin converting enzyme 2 receptor, which is used by SARS-CoV-2 to bind and penetrate into the cell, is widely expressed on the epithelial cells of the mucosa of the oral cavity.[13] These findings could explain the underlying pathogenetic mechanism of taste and olfactory disorders in SARS-CoV-2 infection.

• References

• 1 World Health Organisation (WHO) Coronavirus disease. (COVID-19) outbreak. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
• 2 Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed 2020; 91 (01) 157-160
• 3 Dubé M, Le Coupanec A, Wong AHM, Rini JM, Desforges M, Talbot PJ. Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43. J Virol 2018; 92 (17) e00404-e00418 . Doi: 10.1128/JVI.00404-18
• 4 Sungnak W, Huang N, Bécavin C, Berg M, Network HLB. SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways. ArXiv200306122 Q-Bio. March 13, 2020. Accessed April 6, 2020. https://arxiv.org/abs/2003.0612
• 5 Huang C, Wang Y, Li X. , et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
• 6 Desforges M, Le Coupanec A, Brison E, Meessen-Pinard M, Talbot PJ. Neuroinvasive and neurotropic human respiratory coronaviruses: potential neurovirulent agents in humans. Adv Exp Med Biol 2014; 807: 75-96
• 7 Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020
• 8 Suzuki M, Saito K, Min WP. , et al. Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope 2007; 117 (02) 272-277
• 9 Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China [published online ahead of print, 2020 Apr 10]. JAMA Neurol. 2020;e201127
• 10 Hummel T, Landis BN, Hüttenbrink KB. Smell and taste disorders. GMS Curr Top Otorhinolaryngol Head Neck Surg 2011; 10: Doc04
• 11 van Riel D, Verdijk R, Kuiken T. The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system. J Pathol 2015; 235 (02) 277-287
• 12 Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 2008; 82 (15) 7264-7275
• 13 Xu H, Zhong L, Deng J. , et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020; 12 (01) 8
• 14 Giacomelli A, Pezzati L, Conti F. , et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis 2020; ciaa330
• 15 Spinato G, Fabbris C, Polesel J. , et al. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA 2020 Doi: 10.1001/jama.2020.6771
• 16 Xydacis MS, Dehgani-Mobaraki P, Holbrook HE. , et al. Smell and taste dysfunction in patients with COVID-19. Lancet Infect Dis Published online April 15,2020 Doi: 10.1016/S1473-3099(20)30293-0