COVD-19 disease causes a wide range of respiratory symptoms. One of them is the olfactory disorder, which is also associated with other viral infections. Impaired sense of smell is associated with damage to the respiratory epithelium. Sniffing problems lasting longer than a few days are reported by more than half of patients infected with SARSCov-2 virus. This problem affects the quality of life and may result, among other things, in eating disorders or an increase in exposure to harmful chemicals. The olfactory epithelium, containing receptor cells, is primarily responsible for the proper functioning of the sense of smell. Impaired smell in COVID 19 is associated with damage to the respiratory epithelium. The article is a review of the scientific literature, in which the issues related to the physiology and anatomical structure of the olfactory organ and the influence of SARSCov-2 virus infection on olfactory disorders were discussed

Kożuchowski, Marcin

Prylińska, Monika

English

Akademicka Platforma Czasopism

321Kożuchowski, Marcin, Prylinska-Jaśkowiak, Monika. The proper functioning of the sense of smell and its disturbances on theexample of COVID-19 infection. Journal of Education, Health and Sport. 2022;12(4):321-325. eISSN 2391-8306. DOIhttp://dx.doi.org/10.12775/JEHS.2022.12.04.026https://apcz.umk.pl/JEHS/article/view/40098https://zenodo.org/record/7117857The journal has had 40 points in Ministry of Education and Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 1, 2021. No. 32343.Has a Journal's Unique Identifier: 201159. Scientific disciplines assigned: Physical Culture Sciences (Field of Medical sciences and health sciences); Health Sciences (Field of Medical Sciences and Health Sciences).Punkty Ministerialne z 2019 - aktualny rok 40 punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 1 grudnia 2021 r. Lp. 32343. Posiada Unikatowy Identyfikator Czasopisma: 201159.Przypisane dyscypliny naukowe:Nauki o kulturze fizycznej (Dziedzina nauk medycznych i nauk o zdrowiu); Nauki o zdrowiu (Dziedzina nauk medycznych i nauk o zdrowiu).© The Authors 2022;This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, PolandOpenAccess. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.(http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.The authors declare that there is no conflict of interests regarding the publication of this paper.Received: 01.04.2022. Revised: 26.04.2022. Accepted: 30.04.2022.The proper functioning of the sense of smell and its disturbances on the example ofCOVID-19 infectionMarcin Kożuchowski 1, Monika Prylinska-Jaśkowiak 11. Department of Physiology of Physical Effort and Functional Anatomy,Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń,PolandAbstractCOVD-19 disease causes a wide range of respiratory symptoms. One of them is the olfactorydisorder, which is also associated with other viral infections. Impaired sense of smell isassociated with damage to the respiratory epithelium. Sniffing problems lasting longer than afew days are reported by more than half of patients infected with SARSCov-2 virus. Thisproblem affects the quality of life and may result, among other things, in eating disorders oran increase in exposure to harmful chemicals. The olfactory epithelium, containing receptorcells, is primarily responsible for the proper functioning of the sense of smell. Impaired smellin COVID 19 is associated with damage to the respiratory epithelium. The article is a reviewof the scientific literature, in which the issues related to the physiology and anatomicalstructure of the olfactory organ and the influence of SARSCov-2 virus infection on olfactorydisorders were discussed.Key words: COVID-19, SARSCov- 2, SARSCov- 2 infection, smell disturbances, olfactorydisordersIntroductionSARSCov-2 coronavirus infection causes a number of heterogeneous respiratory symptoms ofextremely varied severity. Ranging from mild symptoms to severe, where severe acuterespiratory failure may develop. [3] Sniffing problems are symptoms that are increasinglyreported in people infected with SARSCoV-2. About half of the patients suffer from anolfactory disorder. Smell disorders have a significant impact on the quality of life. It is relatedto the impaired ability to recognize the smells of food and the environment, which may resultin malnutrition, weight disorders, food poisoning or depression. Equally important is theincrease in exposure to hazardous chemicals. [15] Effective measures to prevent the spread of322SARS-CoV 2 virus are limited, so it is important to recognize the early symptoms ofcoronavirus disease. SARS-CoV infection mainly affects the lungs, it also causes fever, cough,and fatigue. However, there are other symptoms, such as loss of smell, which has beenvalidated by clinicians and the public around the world. [7] This is confirmed by clinical trialsconducted in the United States, Italy and Iran, where olfactory and taste disorders werestrongly associated with COVID-19 infection. It has also been suggested to consider the lossof smell and taste as a subline marker or a possible early symptom of SARS-CoV 2 infection[9] There was also a correlation between the occurrence of olfactory disorders and an increasein mortality from COVID 19. Taking into account the frequency of smell disorders amongCOVID-19 patients, these symptoms were included in the official lists of symptoms ofSARSCoV-2 infection around the world. [15].Anatomy and physiology of smellHuman senses (sight, hearing, touch, taste) are well understood in most cases. On the otherhand, the sense of smell, which is difficult to test, has still not been fully explored. Odorperception is a combination of an orthonosic odor, which is related to the sniffing of a smellof, for example, flowers or food, and a retronosic odor located in the oropharynx. It resultsfrom the flow of air through the nasopharynx during the act of swallowing or exhaling airthrough the nose. [3] Currently, it is believed that the smell is caused by numerous odorreceptors, accumulated on the sensory cilia in the olfactory epithelium [7]. These receptorsactivate the appropriate olfactory centers and transmit a signal to the olfactory cortex in thebrain. [2]. The nasal mucosa has an olfactory neuronepithelium which makes up 1.25% of thenasal mucosa and covers an area of ​ ​ 8 to 10 cm square. This surface consists of theethmoid plate, the upper part of the nasal septum, and the middle and upper turbinates. Thereare approximately 10 million olfactory receptor cell dendrites in the olfactory bulb. The smellreaching the olfactory epithelium dissolves in the mucus layer and then, through a complexreaction, activates the olfactory receptors through complex reactions that require the presenceof fragrance-binding proteins. [3] Sensory cilia are organelles supported by structures calledmicrotubules, which protrude from outside the cell surface. They act as an antenna throughwhich various environmental stimuli are received. The proper functioning of the sense ofsmell requires the proper structure and functioning of the olfactory cells. Hence, anosmiaturns out to be a very common symptom of some types of ciliopathy, for example, Bardet-Biedl syndrome. [13]. One fragrance activates many types of receptors to varying degrees.The olfactory cells transmit chemical information that has the frequency of the emission ofnerve impulses and send it to the olfactory glomeruli. This information is integrated andtransmitted in the olfactory bulb. The olfactory bulb neurites pass into the olfactory pedicle tothe primary olfactory cortex. The information processed in the cortex affects other areas of thebrain, such as: the amygdala, the hypothalamus, the hippocampus, and the olfactory cortex.There are about 350 different genes in the human body coding for specific protein receptors.These receptors interact with selected groups of chemicals, leading to a complex process ofidentifying odors. Viral inflammation of the olfactory epithelium can change the structure ofthe cilia, which disturbs the perception of olfactory cells. [3] According to the OLFACATstudy (OLFAction in Catalonia), loss of smell in the form of hyposmia or anosmia occurs inalmost 20% of Europeans, where the overall population of European Union citizens is around82 million. [12]. On the other hand, epidemiological data of olfactory disorders in the USadult population show that impaired smell is present at the level of 13.5% of the population.For comparison, in the same population, taste impairment occurs in 17.3%, while bothdysfunctions are at the level of 2.2%. [6].323The etiology of olfactory disordersThe main causes of acquired olfactory loss include upper respiratory tract infection such asrhinitis, inflammation of the paranasal sinuses by viruses: adenoviruses, rhinoviruses,coronaviruses, and influenza viruses. Other causes are traumatic brain injury orneurodegenerative diseases: Parkinson's disease, Alzheimer's disease, brain tumors. And alsodrugs, chemicals, radiation, and iatrogenic damage. [5] Loss of smell is a common occurrencein viral infections, especially in the common cold and acute inflammation of the paranasalsinuses. This symptom occurs on average in more than 60% of cases and usually heals itselfafter 3-7 days. However, there are cases of permanent post-viral loss of smell. [4] The loss ofsmell in upper respiratory tract infections is caused by a combination of many factors thatprevent odor transmission. In mucositis as a result of a cytokine storm and neurodegenerationof the olfactory epithelium. [1].Covid-19-related olfactory disordersFirst, the coronavirus infects the ciliary cells of the nasal epithelium, thereby causing the lossof cilia. Bjorn Afzelius detected the coronavirus in macaque ciliary cells. [7]. The sameanimals demonstrated the expression of SARS-CoV-2 in ciliated cells of the nasal epithelium.Coronaviruses enter the host cells via a spike (S) that binds to a specific receptor through aprotease-dependent reaction. The SARS-CoV-2 virus uses the angiotensin converting enzyme2 as the receptor and Transmembrane Serine Protease 2 (TMPRSS2) as the cellular protease.Protease and receptor expression has been described as the primary mechanism by which thecoronavirus infects human nasal epithelial cells. [8,14]. There are currently two models thatexplain how the ciliated epithelial cells of the nasal epithelium are lost. The first is theamputation model in which the thistle is removed completely at the base, as is a suddenchange in pH to remove the Chlamydomonas flagellum. Another model is the absorptionmodel. Cilia can be gradually absorbed by the cytoplasm of the ciliary cell. [10]. Cilia loss isalso seen in other viral infections. Tests using a transmission electron microscope have shownthat shortened cilia regenerate during the patient's recovery, which results in the restoration ofthe sense of smell.SummarySmell disorder is one of the most common symptoms of viral infections, including the SARS-CoV-2 virus. The physiological processes of the sense of smell mechanism and the structureof the anatomical structures responsible for the proper sense of smell are known. Attempts arecurrently underway to explain the causes of olfactory cell damage in the mechanism ofSARS-CoV-2 infection. This will allow the search for effective treatments for chronicolfactory dysfunction in people who have undergone COVID-19. This will contribute to theimprovement of the quality of life due to the restoration of the perception of smells and theimprovement of the protective functions of the smell by faster reaction to chemical hazards.References:1. Butowt R, Bilinska K. SARS-CoV-2: olfaction, brain infection, and the urgent need forclinical samples allowing earlier virus detection. ACS Chem Neurosci. 2020;11(9):1200–3.2. Glezer I & Malnic B (2019) Olfactory receptor function. Handb Clin Neurol 164, 67–78.3243. Izquierdo-Dominguez A, Rojas-Lechuga MJ, Mullol J, Alobid I. Olfactory Dysfunction inthe COVID-19 Outbreak. J Investig Allergol Clin Immunol. 2020;30(5):317-326. doi:10.18176/jiaci.0567. Epub 2020 May 14. PMID: 32406374.4. Jaume F, Quintó L, Alobid I, Mullol J. Overuse of diagnostic tools and medications in acuterhinosinusitis in Spain: a population-based study (the PROSINUS study). BMJ Open. 2018Jan 31;8(1):e018788. doi: 10.1136/bmjopen-2017-018788. PMID: 29391364; PMCID:PMC5878244.5. Klimek, L., Hagemann, J., Alali, A., Spielhaupter, M., Huppertz, T., Hörmann, K., Stielow,S., Freudelsperger, L. and Matthias, C. (2021), Telemedicine allows quantitative measuring ofolfactory dysfunction in COVID-19. Allergy, 76: 868-870. https://doi.org/10.1111/all.14467.6. Liu G, Zong G, Doty RL, Sun Q. Prevalence and risk factors of taste and smell impairmentin a nationwide representative sample of the US population: a cross-sectional study. BMJOpen. 2016;6(11): e013246.7. Li W, Li M, Ou G. COVID-19, cilia, and smell. FEBS J. 2020 Sep;287(17):3672-3676. doi:10.1111/febs.15491. Epub 2020 Aug 6. PMID: 32692465; PMCID: PMC7426555.8. Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, Winter H, Meister M,Veith C, Boots AW et al. (2020) SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarilyexpressed in bronchial transient secretory cells. EMBO J 39, e105114.9. Mehraeen E, Behnezhad F, Salehi MA, Noori T, Harandi H, SeyedAlinaghi S. Olfactoryand gustatory dysfunctions due to the coronavirus disease (COVID-19): a review of currentevidence. Eur Arch Otorhinolaryngol. 2021 Feb;278(2):307-312. doi: 10.1007/s00405-020-06120-6. Epub 2020 Jun 17. PMID: 32556781; PMCID: PMC7297932.10. Mirvis M, Siemers KA, Nelson WJ & Stearns TP (2019) Primary cilium loss inmammalian cells occurs predominantly by whole-cilium shedding. PLoS Biol 17, e3000381.11. Mullol J, Alobid I, Mariño-Sánchez F, Izquierdo-Domínguez A, Marin C, Klimek L, WangDY, Liu Z. The Loss of Smell and Taste in the COVID-19 Outbreak: a Tale of ManyCountries. Curr Allergy Asthma Rep. 2020 Aug 3;20(10):61. doi: 10.1007/s11882-020-00961-1. PMID: 32748211; PMCID: PMC7397453.12. Mullol J, Alobid I, Mariño-Sánchez F, Quintó L, de Haro J, Bernal-SprekelsenM, et al.Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: apopulation-based survey (OLFACAT study). BMJ Open. 2012;2:e001256.13. Reiter JF & Leroux MR (2017) Genes and molecular pathways underpinning ciliopathies.Nat Rev Mol Cell Biol 18, 533–547.14. Sungnak W, Huang N, Becavin C, Berg M, Queen R,Litvinukova M, Talavera-Lopez C,Maatz H, Reichart D, Sampaziotis F et al. (2020) SARS-CoV-2 entry factors are highlyexpressed in nasal epithelial cells together with innate immune genes. Nat Med 26, 681–687.15. Zhang Y, Mei T, Chen Y, Wang L, Jiang L, Liu K, Zhao L, Luo Z, Chi W, Zhu X. Smelldisorders in COVID-19 patients: role of olfactory training: A protocol for systematic review325and meta-analysis. Medicine (Baltimore). 2021 Feb 26;100(8):e24862. doi:10.1097/MD.0000000000024862. PMID: 33663108; PMCID: PMC7909207.

The proper functioning of the sense of smell and its disturbances on the example of COVID-19 infection

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The proper functioning of the sense of smell and its disturbances on the example of COVID-19 infection

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