Modern view on the etiopathogenetic factors in the development of olfactory impairment in COVID-19

Modern view on the etiopathogenetic factors in the development of olfactory impairment in COVID-19

Authors

  • U.N. Vokhidov Tashkent State Dental Institute
  • D.B. Rajabov Tashkent State Dental Institute

Keywords:

anosmia, hyposmia, new coronavirus infection, SARS-CoV-2, COVID-19

Abstract

One of the symptoms of a new coronavirus infection (COVID-19) is a complete or partial violation of the sense of smell. The aim of the review was to explore the mechanisms of olfactory impairment in COVID-19. The review material included scientific publications based on the PubMed database over the past 5 years, which searched for publications on the problem of olfactory impairment in COVID-19. Publication's analysis has shown that the existing ideas about conductive anosmia are insufficient to explain the causes of olfactory impairment caused by SARS-CoV-2. The main hypothesis of olfactory impairment in COVID-19 is that anosmia/hyposmia is caused by damage not to neuronal cells (as previously assumed), but to the olfactory epithelium.

References

Baig A.M., Khaleeq A., Ali U., Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020; 11 (7): 995-8. DOI: https://doi. org/10.1021/acschemneuro.0c00122

Baj J., Karakuta-Juchnowicz H., Teresinski G., et al. COVID-19: specific and non-specific clinical manifestations and symptoms: the current state of knowledge. J Clin Med. 2020; 9 (6): 1753. DOI: https://doi.org/10.3390/jcm9061753

Bilinska K., Butowt R. Anosmia in COVID-19: a bumpy road to establishing a cellular mechanism. ACS Chem Neurosci. 2020; 11 (15): 2152-5. DOI: https://doi. org/10.1021/acschemneuro.0c00406

Bilinska K., Jakubowska P., Von Bartheld C.S., Butowt R. Expression of the SARS-CoV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and trends with age. ACS Chem Neurosci. 2020; 11 (11): 1555-62. DOI: https://doi.org/10.1021/acschemneuro.0c00210

Brann D.H., Tsukahara T., Weinreb C., et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020; 6 (31): 5801. DOI: https://doi. org/10.1126/sciadv.abc5801

Brann J.H., Firestein S.J. A lifetime of neurogenesis in the olfactory system. Front Neurosci. 2014; 8: 182. DOI: https://doi.org/10.3389/fnins.2014.00182

Brechbuhl J., Lopes A.C., Wood D., et al. Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms. Commun Biol. 2021; 4 (1): 880. Epub 2021 Jul 15. DOI: https:// doi.org/10.1038/s42003-021-02410-9

Briguglio M., Giorgino R., Dell'Osso B., et al. Consequences for the elderly after COVID-19 isolation: FEaR (Frail Elderly amid Restrictions). Front Psychol. 2020; 11: 56-9. DOI: https://doi.org/10.3389/fpsyg.2020.565052

Bryche B., St Albin A., Murri S., et al. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun. 2020; 89: 579-86. DOI: https://doi. org/10.1016/j.bbi.2020.06.032

Butowt R., Bilinska K. SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem Neurosci. 2020; 11 (9): 1200-3. DOI: https://doi.org/10.1021/acschemneuro.0c00172

Butowt R., von Bartheld C.S. Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist. 2021; 27 (6): 582-603. DOI: https://doi.org/10.1177/1073858420956905

Cazzolla A.P., Lovero R., Lo Muzio L., et al. Taste and smell disorders in COVID-19 patients: role of interleukin-6. ACS Chem Neurosci. 2020; 11 (17): 2774-81. DOI: https://doi.org/10.1021/acschemneuro.0c00447

Das G., Mukherjee N., Ghosh S. Neurological insights of COVID-19 pandemic. ACS Chem Neurosci. 2020; 11 (9): 1206-9. DOI: https://doi.org/10.1021/ acschemneuro.0c00201

de Melo G.D., Lazarini F., Levallois S., et al. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Sci Transl Med. 2021; 13 (596): eabf8396. DOI: https:// doi.org/10.1126/scitranslmed.abf8396

Dell'Era V., Farri F., Garzaro G., Gatto M., Aluffi Valletti P., Garzaro M. Smell and taste disorders during COVID-19 outbreak: cross-sectional study on 355 patients. Head Neck. 2020; 42 (7): 1591-6. DOI: https://doi.org/10.1002/hed.26288

Dos Santos M.F., Devalle S., Aran V., et al. Neuromechanisms of SARS-CoV-2: a review. Front Neuroanat. 2020; 14: 37. DOI: https://doi.org/10.3389/ fnana.2020.00037

Doty R.L., Mishra A. Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis [published correction appears in Laryngoscope 2001; 111 (9): 1673]. Laryngoscope. 2001; 111 (3): 409-23. DOI: https://doi. org/10.1097/00005537-200103000-00008

Eliezer M., Hamel A.L., Houdart E., et al. Loss of smell in patients with COVID-19: MRI data reveal a transient edema of the olfactory clefts. Neurology. 2020; 95 (23): e3145-52. DOI: https://doi.org/10.1212/WNL.0000000000010806

Eliezer M., Hautefort C. MRI evaluation of the olfactory clefts in patients with SARS-CoV-2 infection revealed an unexpected mechanism for olfactory function Loss. Acad Radiol. 202; 27 (8): 1191. DOI: https://doi.org/10.1016/j.acra.2020.05.013

Eliezer M., Hautefort C., Hamel A., et al. Sudden and complete olfactory loss of function as a possible symptom of COVID-19. JAMA Otolaryngol Head Neck Surg. 2020; 146 (7): 674-5. DOI: https://doi.org/10.1001/jamaoto.2020.0832

Eshraghi A.A., Mirsaeidi M., Davies C., Telischi F.F., Chaudhari N., Mittal R. Potential mechanisms for COVID-19 induced anosmia and dysgeusia. Front Physiol. 2020; 11: 1039. DOI: https://doi.org/10.3389/fphys.2020.01039

Gane S.B., Kelly C., Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020; 58 (3): 299-301. DOI: https://doi. org/10.4193/Rhin20.114

Gupta K., Mohanty S.K., Mittal A., et al. The cellular basis of loss of smell in 2019-nCoV-infected individuals. Brief Bioinform. 2021; 22 (2): 873-81. DOI: https://doi.org/10.1093/bib/bbaa168

Hummel T., Whitcroft K.L., Andrews P., et al. Position paper on olfactory dysfunction. Rhinol Suppl. 2017; 54 (26): 1-30. DOI: https://doi.org/10.4193/ Rhino16.248

Islamoglu Y., Gemcioglu E., Ates I. Objective evaluation of the nasal mucosal secretion in COVID-19 patients with anosmia. Ir J Med Sci. 2021; 190: 889-91. DOI: https://doi.org/10.1007/s11845-020-02405-1

Jalessi M., Barati M., Rohani M., et al. Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19. Neurol Sci. 2020; 41 (9): 2331-8. DOI: https://doi.org/10.1007/s10072-020-04590-4

Jia H., Rochefort N.L., Chen X., Konnerth A. Dendritic organization of sensory input to cortical neurons in vivo. Nature. 2010; 464 (7293): 1307-12. DOI: https:// doi.org/10.1038/nature08947

Kandemirli S.G., Altundag A., Yildirim D., Tekcan Sanli D.E., Saatci O. Olfactory bulb MRI and paranasal sinus CT findings in persistent COVID-19 anosmia. Acad Radiol. 2021; 28 (1): 28-35. DOI: https://doi.org/10.1016/j.acra.2020. 10.006

Kaye R., Chang C.W.D., Kazahaya K., Brereton J., Denneny J.C. COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg. 2020; 163 (1): 132-4. DOI: https://doi.org/10.1177/0194599820922992

Kerslake R., Hall M., Randeva H.S., et al. Co-expression of peripheral olfactory receptors with SARS-CoV-2 infection mediators: potential implications beyond loss of smell as a COVID-19 symptom. Int J Mol Med. 2020; 46 (3): 949-56. DOI: https:// doi.org/10.3892/ijmm.2020.4646

Lechien J.R., Chiesa-Estomba C.M., De Siati D.R., 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 (8): 2251-61. DOI: https://doi.org/10.1007/s00405-020-05965-1

Lu Y., Li X., Geng D., et al. Cerebral micro-structural changes in COVID-19 patients - an MRI-based 3-month follow-up study. EClinicalMedicine. 2020; 25: 100484. DOI: https://doi.org/10.1016/j.eclinm.2020.100484

Meinhardt J., Radke J., Dittmayer C., et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021; 24: 168-75. DOI: https://doi.org/10.1038/s41593-020-00758-5

Meng X., Pan Y. COVID-19 and anosmia: the story so far. Ear Nose Throat J. 2021. DOI: https://doi.org/10.1177/01455613211048998

Mi B., Chen L., Xiong Y., Xue H., Zhou W., Liu G. Characteristics and early prognosis of COVID-19 infection in fracture patients. J Bone Joint Surg Am. 2020; 102 (9): 750-8. DOI: https://doi.org/10.2106/JBJS.20.00390

Nakagawara K., Masaki K., Uwamino Y., et al. Acute onset olfactory/taste disorders are associated with a high viral burden in mild or asymptomatic SARS-CoV-2 infections. Int J Infect Dis. 2020; 99: 19-22. DOI: https://doi.org/10.1016/ j.ijid.2020.07.034

Printza A., Constantinidis J. The role of self-reported smell and taste disorders in suspected COVID-19. Eur Arch Otorhinolaryngol. 2020; 277 (9): 2625-30. DOI: https://doi.org/10.1007/s00405-020-06069-6

Schwob J.E. Neural regeneration and the peripheral olfactory system. Anat Rec. 2002; 269 (1): 33-49. DOI: https://doi.org/10.1002/ar.10047

Sen A. Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19? Med Hypotheses. 2021; 153: 110627. DOI: https://doi.org/10.1016/j.mehy.2021.110627

Sia S.F., YalLM., Chin A.W.H., et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature. 2020; 583: 834-8. DOI: https://doi.org/10.1038/ s41586-020-2342-5

Singh M., Bansal V., Feschotte C. A single-cell RNA Expression map of human coronavirus entry factors. Cell Rep. 2020; 32 (12): 108175. DOI: https:// doi.org/10.1016/j.celrep.2020.108175

Spinato G., Fabbris C., Polesel J., et al. Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA. 2020; 323 (20): 208990. DOI: https://doi.org/10.1001/jama.2020.6771

Vaira L.A., Salzano G., Deiana G., De Riu G. Anosmia and ageusia: common findings in COVID-19 patients. Laryngoscope. 2020; 130 (7): 1787. DOI: https://doi. org/10.1002/lary.28692

Wang D., Hu B., Hu C., et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China [published correction appears in JAMA. 2021; 325 (11): 1113]. JAMA. 2020; 323 (11): 1061-9. DOI: https://doi.org/10.1001/jama.2020.1585

Wang M., et al. Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan. MedRxiv. 2020. URL: http:/www.medrxiv.org/content/10.1101/2020.02.-12.20022327v2

Yildirim D., Kandemirli S.G., Tekcan Sanli D.E., Akinci O., Altundag A. A comparative olfactory MRI, DTI and fMRI study of COVID-19 related anosmia and post viral olfactory dysfunction. Acad Radiol. 2022; 29 (1): 31-41. DOI: https://doi. org/10.1016/j.acra.2021.10.019

Zhang J.J., Dong X., Cao Y.Y., et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020; 75 (7): 1730-41. DOI: https://doi.org/10.1111/all.14238

Published

2023-10-20

Issue

Section

Articles
Loading...