Loss of Taste, Smell and Oral Mani festations in COVID-19

1. Abstract COVID 19 mainly affects the respiratory, gastrointestinal and neurologicalsystemsbutitalsoinvolvestheoralcavity,olfactory and integumentary system.The oral manifestations of COVID 19 along with inflammatory response of surrounding tissues are due toangiotensinconvertingenzymes(ACE2)andTransmembrane serine protease (TMPRSS 2). ACE 2 and TMPRSS 2 play a key roleinvirustransmissionthroughsalivaandshowsitsexpression in the salivary glands, oral mucosal epithelium.The reported oral manifestation of COVID 19 are Xerostomia, loss of taste, smell, COVID tongue, halitosis and mucosal lesions. The exact mechanismhowthesestructuresareinvolvedarenotknownthatwhether thesemanifestationsaretheresultofdirectinfectionorsecondary manifestations.Thisreviewwilldiscusstheoralmanifestationsof COVID 19 along with its possible mechanism.

2. Introduction SARS-CoV-2 is a pandemic infectious disease threatening the World today [1] having many clinical manifestations such as fever, dry cough, viral pneumonia, shortness of breath, myalgia, headache,sorethroat,rhinorrhea,chestpain,nausea,vomitingand diarrhea,conjunctiva,nasalcongestion,fatigue,Hemoptysis,chill, lossoftasteandsmell.SARS-CoV-2caninfectthemouth,raising thepossibilitythatsalivacanplayamajorroleinthetransmission ofvirus.ThusoralcavityisimportantsiteforSARS-CoV-2[2, 3]. Theresearchershypothesizedthatsalivaryglands,barrierepithelialcellsoftheoralcavityandoropharynxcanbeinfectedbySARSCitation: AkhtarQJ,LossofTaste,SmellandOralManifestations in COVID-19. Ann Clin Med Case Rep. 2022;V10(8):1-4 CoV-2contributingtothespreadoftheinfection.Twohumanoral single–cellRNAsequencing(ScRNA–seq)atlasestopredictcell specific susceptibilities to SARS-CoV-2 infection. RNA or two keyviralentryproteinstheACE2andTMPRSS2arefoundinthe salivary gland and lining of the oral cavity plus in gingival cells indicatinghighervulnerabilitytoSARS-CoV-2infection.Thereis correlation between oral symptoms and saliva containing SARSCoV-2suggestingoralinfectionmayplayaroleinCOVID19oral symptoms [4, 5]. Thus mouth is considered as prime site for COVID 19 infection evenbeforesymptomsandtheoccurrenceoflossoftaste(aguesia) andlossofsmelloccurinmanypatients.Theseorallesionsdueto COVID 19 occur in both gender approximately 52 years of age. The ulcerated lesions are most common may be erosions, petechial, macules and blisters.The main site is palate and the tongue followedbygumsandthelips.ThereisOrofacialpainin75%cas- es while taste alterations occur in 25% of the reported cases. The exact etiology of these manifestations are unknown but may be multifactorial it may be due to direct or indirect action of SARSCoV-2 over oral mucosa to cells to the hypersensitivity of drugs used in the treatment of COVID 19 or general state of health of patient due to disease or to long period of hospitalization. Oral manifestations due to hypersensitivity reactions of drugs are not unknown in case of COVID 19 but may be due to the cytokines storm [6]. Salivaisacommontransientmediumfortransmittingvirus by breathing, talking and sneezing by droplets. It can pass on the infection this indicates that saliva as a potential route of SARSCoV-2transmissionandcanbeusedfordiagnosisofCOVID19 - a reliable tool to detection of SARS-COV-2 [7]. The COVID19 also migrates from the naso pharynx to the lower respiratory tracttotheoralcavitybutitcan’tbeexcludedthatarolemay be played by the secretary activity of salivary gland.As There is highexpressionofACE2receptorsof2019-nCOVontheepithe- lial cells of oral mucosa with high tendency on tongue (13 times) thisACE2 expressing cells in oral tissues especially in epithelial cells of tongue than mucosal and gingival tissues might pass vide possiblerouteofenteringfor2019-n-COVwhichprovesthatoral cavity might be potential risk route of 2019-n-COV [8]. There appear many oral manifestations in Corona patients which may be due to predisposing factors such as poor oral hygiene, stress, opportunistic infection, immunosuppression, vasculitis, hyper inflammatory response secondary to COVID 19. There is oral dryness, Vesiculo bullous lesions, Aphthous like ulceration, Dysguesiaandanosmia[9].Themainstimulantsoftastearesaliva formationXerostomiamaybecausedinnasalcongestionandrhinorrheawhichleadtodysguesia[10].Xerostomiaalsocontributes to burning mouth syndrome. The Corona patients also complain of fore head pain which is explainedbypatientsasinabilitytodifferentiatebetweenfacialpain andheadache.ItisduetonasalcongestionwhichoccursinURTI as result of dilatation of veins in the nasal epithelium with added secretionsinthesinuseswhichputspressureintrigeminalnerves endingscausingpain.ThebruxismduetostressandpsychoemotionalstatusinCOVID19resultinTMDsymptomswithOrofacial pain [11]. There are taste buds widely distributed in the oral cavity containing taste receptors but mainly concentrated in the papilla on the dorsum of tongue with ACE2 which are diffusely expressed on the mucous membrane of the whole oral membrane [12]. There areACE2receptorsonthetonguetowhichSARS-Cov-2bindsas compared to buccal and gingival tissues of oral cavity in order to gainentryintohostcells/highlyexpressedintheepithelialcellsof tonguehenceitcouldbepossiblereasonfortastedisturbanceinall viralinfectionsincludingCOVID19infection[13].TheTasteloss can occur due to damage of to taste pores because of the destruc- tion of taste buds. Lossoftastecanbeduetodamageofneuralpathwayinnervating the taste buds subsequent to viral infection in the oral cavity asthe cranial nerve V11,1X an X which transmit information from mouthandpharynxtobrainareinvolved.Tastelosscanoccurdue todamageoftasteporesbecauseofthedestructionorlossoftaste buds .Corona virus binds to their target cell through angiotensin convertingenzyme2(ACE2)whicharealsoexpressedbyepithelialcellsofthelungs,intestine,Kidneys,bloodvesselssoaffecting thesesystemsofthebodyTheenzymeTMPRSS(transmembrane protease,serine2)allowsthevirustofusetomembranewiththatof host cell and slip inside [14]. The general health state of the COVID 19 patients are degraded which predisposes the appearance of oral manifestations.The patients are hospitalized and different procedures are performed the opportunist infections such as thrush and herpes so oral care hygiene is important in hospitalization. The Oral lesions in diagnosis of COVID 19 are controversial. TastealterationsmaybeconsideredmostrelevantoralmanifestationsoffCOVID19.OrallesionsduetoCOVID19occurinboth genders approximately 52 years of age. (2, 15) The ulcerated lesionsaremostcommonwhichmaybeerosions,petechial,macules and blisters.The main site is palate and tongue followed by gums andthelips.Thereispainin75%whiletastealterationsin25%of reported cases. ThemostlyreportedfiveoralmanifestationsassociatedwithCOV- ID 19 are as under: 1. Gingivalinflammation.Thisisduetocytokinestormparticular- ly interleukin 6 (IL 6) 2. Xerostomia (Dry mouth) There are many causes of Xerostomia such as auto immune diseases drugs, viral infection and now COVID19.Xerostomiamaycauseoralulceration,halitosiscaries and fungal infection, candidiasis.The quantity and quality of salivary flow is decreased in corona due to viral entry into salivary gland [16]. 3. COVIDTongue The association between erythema migrans (Geographic tongue) and SARS-CoV-2 is termed as COVID tongue [17]. Geograph-ic tongue is a benign condition which has positive association between SARS-CoV-2. In COVID tongue there is swelling with bumps on the left side and swelling with patchy red spot on the rightsideoftongue.COOVIDtongueistheresultofinflameddiseaseACE2receptorsenzymesthatactaspointofentryforSARS- CoV2 AND exist in large number on the tongue and mucous membrane o mouth resulting in swelling, bumps and patchiness associatedwithCOVIDtongue[18].Theothertheoryiscoronaviruscausesinflammationofbloodvesselsandthevirusismessing with blood vessels in the tongue and mouth resulting in COVID tongue so much research is needed. The COVID tongue has two types of symptoms: Patient may complain of discoloration, enlargement and other mouth problems “Furry coating” can be white or yellow cannot be scrubbed of with brush, Scalloped tongue which is painful; the other group hadinflammationofsmallbumpsontonguesurfacewhichmaybe swollenandinflamed,mouthulcersandpatchyareaontongueand swelling in mouth [19, 20]. 4. Cracked teeth There is increase in bruxism due to stress sleep deprivation or obstructive sleep apnea result in cracked teeth and bruxism with TMD and Orofacial pain [21, 22].

5. Loss of taste and smell which observed in many patients with COVVID 19 but not clear that these manifestations are due to Covid 19 or secondary manifestations due to patients systemic conditions. ACE2 receptors which are diffusely expressed on the mucous membraneofthewholeoralcavityparticularlyonthetongue.The role ofACE2 in modulating taste perception due to chemo sensi- tive side effects ofACE2 inhibitors and angiotensin 11 blockers. There is reduction in sialic acid in saliva which is a fundamental component of salivary mucin and its glycoprotein s that convey gustatorymoleculeinsidetasteporefromprematureenzymedegradation,sothereisanincreasegustatorythreshold,SAR-CoV-2 occupy the binding sites of sialic acid on taste buds accelerating degradationofgustatoryparticlesplusolfactorydisturbancesViral disruption of cranial nerves 1,7,9and 10 as well as the supporting cells of neural transmission [23]. The inflammation can induce expression ofACE2 in human cells notneuronmightunderrepresentthecellstypesthatexpressACE2 under CoV -2 INFECTIONAbundance ofACE2 receptor direct.

3. Anosmia(LossofSmell) The loss of smell result from diseases which causes the diseaseof pathways which transmit smell to the brain by use of drugs as decongestants,nasalsprays,nifedipineandprothiazines. There is close relationship between taste and smell as olfactory sensory neurons, sensory cells detect odors and these neurons are present in nasal lining. The infection or swelling of these blockage prevent odor massages to the brain.The ability to taste food is tiedly connected to sense of smell so there is loss of taste [24, 25]. The tongueisthenotonlyanorganinvolvedintastebutthroat,roofof mouthandnose.Lossoftastealsooccurinupperrespiratorytract such as common cold, sinus infection, middle ear infection, poor oral hygiene, anti-fungal drugs, macrolides, proton pump inhibi- tors, ACE ect also affect the person ability to taste. Taste disturbances mainly occur in oral infection, oral appliance such as dentures, bell’s palsy and old age. It is an early warning system against toxins, polluted air, smoke and spoiled food products. It has significant impact on quality o lie.Taste receptors are in taste buds not only on the tongue but also on the soft palate, pharynx, epiglottis, uvula and first one third of esophagus. These are bathed by salivary gland and dryness distort perception. The exact etiology or loss of smell is unknown the damage of olfactory system is either due to primary infection or secondary inflammation.ItispossiblethatcellsinfectedwithCOV-2canform syncytia with cells that do not express the ACE2 such a mechanismcandamageneuronadjacenttoinfectedcells.Theinflamma- tion can induce expression of expression ofACE2 in human cells sostemcellsnotneuronsmightunderrepresentthecellstypesthat express ACE2 under COV -2 [26].

4. Conclusion LossoftasteandsmellisfirstrecognizedsymptomofCOVID19 butmostcommonoralsymptomsareonthetongue,aphthouslike ulcers,herptiformlesions,Xerostomiaandcandidiasiswhichoc- cur in old people either due to previous underlying disease stress, trauma,hyperinflammatoryresponseofCOVID19ordrugaller- gy which may be aggravating factor in the development of oral lesions.

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QaziJaved Akhtar. Loss of Taste, Smell and Oral Mani festations in COVID-19. Annals of Clinical and Medical Case Reports 2022