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      Characteristics Associated with Olfactory and Taste Disorders in COVID-19

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          Abstract

          Introduction

          Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks.

          Methods

          Two retrospective cohort studies were conducted in a high school and primary schools of Northern France following a COVID-19 epidemic in February-March 2020. Students, their relatives, and school staff were included. Anti-SARS-CoV-2 antibodies were identified using a flow-cytometry-based assay detecting anti-S IgG.

          Results

          Among 2,004 participants (median [IQR] age: 31 [11–43] years), 303 (15.2%) tested positive for SARS-CoV-2 antibodies. OTDs were present in 91 (30.0%) and 92 (30.3%) of them, respectively, and had 85.1 and 78.0% positive predictive values for SARS-CoV-2 infection, respectively. In seropositive participants, OTDs were independently associated with an age above 18 years, female gender, fatigue, and headache.

          Conclusion

          This study confirms the higher frequency of OTDs in females than males and adults than children. Their high predictive value for the diagnosis of COVID-19 suggests that they should be systematically searched for in patients with respiratory symptoms, fever, or headache. The association of OTDs with headache, not previously reported, suggests that they share a common mechanism, which deserves further investigation.

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          Most cited references39

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          High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

          It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.
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            Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

            The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.
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              Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study

              To the Editor—We read with interest the article by Wang et al [1] describing the clinical features of 69 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, China. The authors provide a detailed description of major signs and symptoms of overt disease [2, 3], but fail to give an account of minor symptoms that may be present at earlier stages of the infection. After some patients admitted for coronavirus disease 2019 (COVID-19) at the Infectious Disease Department of L. Sacco Hospital in Milan, Italy, complained of olfactory and taste disorders (OTDs), we performed a cross-sectional survey of the prevalence of these alterations in the context of SARS-CoV-2 infection. On 19 March 2020, a simple questionnaire including questions about the presence or absence of OTDs, their type and time of onset respective to hospitalization were submitted through verbal interview to all SARS-CoV-2–positive hospitalized patients who were able to give informed consent. Of 88 hospitalized patients, 59 were able to be interviewed (29 were nonrespondents, of whom 4 had dementia, 2 had a linguistic barrier, and 23 were on noninvasive ventilation) (Table 1). Of these, 20 (33.9%) reported at least 1 taste or olfactory disorder and 11 (18.6%) both. Twelve patients (20.3%) presented the symptoms before the hospital admission, whereas 8 (13.5%) experienced the symptoms during the hospital stay. Taste alterations were more frequently (91%) before hospitalization, whereas after hospitalization taste and olfactory alteration appeared with equal frequency. Females reported OTDs more frequently than males (10/19 [52.6%] vs 10/40 [25%]; P = .036). Moreover, patients with at least 1 OTD were younger than those without (median, 56 years [interquartile range {IQR}, 47–60] vs 66 [IQR, 52–77]; P = .035). All patients reported the persistence of OTDs at the time of the interview. Table 1. Characteristics of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Assessed for Taste and Olfactory Disorders (N = 59) Patients No. (%) Age, y, median (IQR) 60 (50–74) Male sex 40 (67.8) Days from illness onset to hospital admission, median (IQR) 6 (4–10) Days from illness onset to the interview, median (IQR) 15 (10–21) Pneumonia at hospital admission 43 (72.8) Symptoms at hospital admission  Fever 43 (72.8)  Cough 22 (37.3)  Dyspnea 15 (25.4)  Sore throat 1 (1.7)  Arthralgia 3 (5.1)  Coryza 1 (1.7)  Headache 2 (3.4)  Asthenia 1 (1.7)  Abdominal symptoms 5 (8.5) No taste or olfactory disorders 39 (66.1) With olfactory and/or taste disorders 20 (33.9) Taste disorders only  Dysgeusia 5 (8.5)  Ageusia 1 (1.7) Olfactory disorders only  Hyposmia 3 (5.1)  Anosmia 0 (0) Mixed taste and olfactory disorders  Dysgeusia and hyposmia 2 (3.4)  Dysgeusia and anosmia 2 (3.4)  Ageusia and hyposmia 2 (3.4)  Ageusia and anosmia 5 (8.5) Data are presented as no. (%) unless otherwise indicated. Abbreviations: IQR, interquartile range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Olfactory and taste disorders are well known to be related with a wide range of viral infections [4, 5]. SARS-CoV has demonstrated in a mice model a transneural penetration through the olfactory bulb [6]. Moreover, angiotensin-converting enzyme 2 receptor, which is used by SARS-CoV-2 to bind and penetrate into the cell, is widely expressed on the epithelial cells of the mucosa of the oral cavity [7]. These findings could explain the underlying pathogenetic mechanism of taste and olfactory disorders in SARS-CoV-2 infection. Due to limitations related to the diffusivity of the disease and emergency contingencies, it was impossible to perform a more structured questionnaire associated with validated tests (ie, Pennsylvania smell identification test) [8]. However, our survey shows that OTDs are fairly frequent in patients with SARS-CoV-2 infection and may precede the onset of full-blown clinical disease. In a pandemic context, further investigations on nonhospitalized infected patients are required to ascertain if these symptoms, albeit unspecific, may represent a clinical screening tool to orientate testing of pauci-symptomatic individuals.

                Author and article information

                Journal
                Neuroepidemiology
                Neuroepidemiology
                NED
                Neuroepidemiology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                0251-5350
                1423-0208
                1 July 2021
                : 1-6
                Affiliations
                [1] aEmerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France
                [2] bVirus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France
                [3] cUMR 3569, Centre National de la Recherche Scientifique (CNRS), Paris, France
                [4] dUniversité de Paris, Sorbonne Paris Cité, Paris, France
                [5] eDirection de la recherche médicale, Institut Pasteur, Paris, France
                [6] fICAReB platform (Clinical Investigation & Access to Research Bioresources) of the Center for Translational Sciences, Institut Pasteur, Paris, France
                [7] gCenter for Translational Sciences, Institut Pasteur, Paris, France
                [8] hVaccine Research Institute, Créteil, France
                [9] iPACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
                Author notes
                Article
                ned-0001
                10.1159/000517066
                8339025
                34198303
                35373915-4d97-4ea8-b437-cab223d68dda
                Copyright © 2021 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 30 January 2021
                : 4 May 2021
                Page count
                Figures: 1, Tables: 1, References: 23, Pages: 6
                Categories
                Original Paper

                Neurosciences
                covid-19,severe acute respiratory syndrome coronavirus-2,anosmia,ageusia,headache
                Neurosciences
                covid-19, severe acute respiratory syndrome coronavirus-2, anosmia, ageusia, headache

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