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      Anosmia: an evolution of our understanding of its importance in COVID-19 and what questions remain to be answered

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          Abstract

          Background

          From the start of the pandemic, many European otolaryngologists observed an unprecendented number of anosmic patients. Early reports proposed that anosmia could be the first or even the only symptom of COVID-19 infection, prompting calls for self-isolation in affected patients.

          Methods

          In the present article, we review the COVID-19 anosmia literature and try to answer the following two questions: first, why is COVID-19 infection responsible for such a high incidence of anosmia? Second, in patients with more severe forms is anosmia really less prevalent and why?

          Results

          In terms of the etiology of olfactory dysfunction, several hypotheses were proposed at the outset of the pandemic; that olfactory cleft inflammation and obstruction caused a localized conductive loss, that there was injury to the sustentacular supporting cells in the olfactory epithelium or, given the known neurotropic potential of coronavirus, that the virus could invade and damage the olfactory bulb. Olfactory cleft obstruction may contribute to the olfactory dysfunction in some patients, perhaps most likely in those that show very early resolution, it cannot account for the loss in all patients.

          Moreover, disordered regrowth and a predominance of immature neurons have been shown to be associated with parosmia, which is a common finding amongst patients with Covid-related anosmia. A central mechanism therefore certainly seems to be consistent with the group of patients with more prolonged olfactory deficits. Sustentacular cells showing ACE-2 immunohistochemical expression 200 to 700 times greater than nasal or tracheal epithelia seem to be the main SARS-CoV-2 gateway.

          As the pathophysiology of COVID-19 anosmia seems to be better understood, the question of why patients with a moderate to severe form of COVID-19 infection have less olfactory involvement remains unresolved. Different potential explanations are discussed in this review.

          Conclusions

          The last 5 months have benefited from great international collaborative research, first highlighting and then proving the value of loss of smell and taste as a symptom of COVID-19. Adoption of loss of smell into the case definition by international public health bodies will facilitate control of disease transmission.

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          Most cited references24

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          Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2

          Journal of Virology, 82(15), 7264-7275
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            Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study

            Objective To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Methods Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). Results A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Conclusion Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection. Electronic supplementary material The online version of this article (10.1007/s00405-020-05965-1) contains supplementary material, which is available to authorized users.
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              Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults

              This study compares angiotensin-converting enzyme 2 ( ACE2 ) gene expression, which has been associated with SARS-CoV-2 cell entry, in the nasal epithelium of children vs adults.
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                Author and article information

                Contributors
                Sven.saussez@umons.ac.be
                Journal
                Eur Arch Otorhinolaryngol
                Eur Arch Otorhinolaryngol
                European Archives of Oto-Rhino-Laryngology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0937-4477
                1434-4726
                9 September 2020
                : 1-5
                Affiliations
                [1 ]COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France
                [2 ]GRID grid.8364.9, ISNI 0000 0001 2184 581X, Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, , University of Mons (UMons), ; Mons, Belgium
                [3 ]GRID grid.4989.c, ISNI 0000 0001 2348 0746, Department of Otorhinolaryngology and Head and Neck Surgery, CHU Saint-Pierre, School of Medicine, , CHU de Bruxelles, Université Libre de Bruxelles, ; Brussels, Belgium
                [4 ]Department of Otolaryngology-Head and Neck Surgery, School of Medicine, UFR Simone Veil, Foch Hospital, Université Versailles Saint-Quentin-en-Yvelines (Paris Saclay University), Paris, France
                [5 ]GRID grid.420545.2, Guy’s and St Thomas NHS Foundation Trust, ; London, UK
                [6 ]British Rhinological Society (President), London, UK
                Author information
                http://orcid.org/0000-0002-3655-1854
                Article
                6285
                10.1007/s00405-020-06285-0
                7480210
                32909060
                2277f572-aa6c-4a2a-9918-697852fea2f1
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 8 July 2020
                : 10 August 2020
                Categories
                Review Article

                Otolaryngology
                smell,olfactory,covid-19,coronavirus,anosmia
                Otolaryngology
                smell, olfactory, covid-19, coronavirus, anosmia

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