key: cord-355422-c4odhdql authors: Vaira, Luigi Angelo; Salzano, Giovanni; Fois, Alessandro Giuseppe; Piombino, Pasquale; De Riu, Giacomo title: Potential pathogenesis of ageusia and anosmia in COVID‐19 patients date: 2020-04-27 journal: Int Forum Allergy Rhinol DOI: 10.1002/alr.22593 sha: doc_id: 355422 cord_uid: c4odhdql From the first reports, ageusia and anosmia appear to be frequent clinical features in coronavirus disease 19 (COVID‐19) patients. We have performed a survey of the literature, analyzing the possible causes of these chemosensory alterations, which may be useful as a starting point for specific further studies. This article is protected by copyright. All rights reserved 19.4% to 88% of patients [1] [2] [3] [4] . The exact pathogenesis of these chemonsensitive disorders has not yet been clarified. At the same time, the comprehension of these mechanisms could be fruitful to understand the way in which the virus spreads through the organism. This article is protected by copyright. All rights reserved. 3 We report our survey of the literature up to April 14, 2020 , analyzing the possible causes of these chemosensory alterations, which may be useful as a starting point for specific future studies. There are no studies in the literature regarding the possible relationship between coronavirus and the development of taste disorders. Angiotensin-converting enzyme 2 (ACE2) has been identified as the cellular receptor for SARS-CoV-2 5 . ACE2 receptors are expressed diffusely on the mucous membrane of the whole oral cavity, particularly on the tongue 6 . The role of ACE2 in modulating taste perception has been highlighted in many studies analyzing the chemosensitive side effects of ACE2 inhibitors and angiotensin II blockers 7, 8 . The mechanism by which ACE2 inhibitors cause taste disturbance is unclear but does not appear to be related to any alteration in serum 7, 8 and saliva 7 zinc levels. Presumably, these drugs inactivate the G-protein-coupled proteins and sodium-ion channels present in the taste receptors 5 . The taste disturbance generally regresses after the suspension of treatment 8 . Moreover, the Middle East Respiratory Syndrome (MERS) coronavirus may bind to the sialic acid receptors 9 , an ability which has also recently been described for SARS-CoV-2 10 . Sialic acid is a fundamental component of the salivary mucin, and it protects the glycoproteins that convey gustatory molecules inside the taste pores from premature enzymatic degradation 11 . A reduction of sialic acid in the saliva is associated with an increase in the gustatory threshold 12 . In such a way, SARS-CoV-2 could therefore occupy the binding sites of sialic acid on the taste buds, accelerating the degradation of the gustatory particles. This article is protected by copyright. All rights reserved. 4 Another possibility is that the ability to perceive flavors in these patients is adversely affected by the concomitant presence of olfactory disturbances, due to the intimate functional correlation between these two chemosensory systems 13 18, 19 . Accordingly, the virus may carry out its damage at the level of the olfactory bulb rather than the epithelium. However, the coronavirus used in these studies has been laboratory modified to target specifically the olfactory bulb. This is not necessarily the same for SARS-CoV-2, which we know has different organ targets. In conclusion, from the first reports 1-4 , ageusia and anosmia appear to be a frequent clinical feature during COVID-19. The pathogenic mechanism underlying the chemosensitive disorders in these patients has not yet been clarified. In our opinion, three lines of research could be useful to provide important indications regarding some still unclear pathogenic aspects. First, it will be necessary to obtain clinical data on large patient cohorts to determine the exact frequency of these symptoms and monitor their recovery over time. Secondly, it may be useful to evaluate the correlation between the viral load in the nasopharyngal swab and the extent of these chemosensitive disorders. Concluding, the histopathological analysis on samples obtained from patients who have died due to COVID-19 will be crucial to understand the nature and location of the olfactory dysfunction. Competing interests: none Sponsorships: none This article is protected by copyright. All rights reserved. None declared. 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