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      Auditory Disturbances and SARS-CoV-2 Infection: Brain Inflammation or Cochlear Affection? Systematic Review and Discussion of Potential Pathogenesis

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          Abstract

          Patients affected by COVID-19 present a series of different symptoms; despite some of these are common, other less likely appear. Auditory symptoms seem to be less frequent, maybe because rarer or, alternatively, because they are underestimated during the clinical investigation. The hearing impairment might be related to the central or peripheral involvement of the auditory pathways; in particular, the likelihood of thrombosis might be one of the causes. To date, the prevalence of auditory symptoms such as sudden or progressive sensorineural hearing loss and tinnitus is unclear in COVID-19 patients. However, their presence might be an early sign of thrombosis or spread of the infection into the brain. In this systematic review of the literature we investigated the presence of auditory symptoms in COVID-19 patients and discussed their potential origin and causal relationship with SARS-CoV-2. Results showed that, despite rarely, auditory impairment can appear in patients with COVID-19 and should always be investigated for an early treatment and potential indicator of involvement of the central nervous system.

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          Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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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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              Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

              Abstract: Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                04 August 2021
                2021
                04 August 2021
                : 12
                : 707207
                Affiliations
                [1] 1Department of Medicine, Surgery and Dentistry, University of Salerno , Salerno, Italy
                [2] 2Department of Sense Organs, Sapienza University of Rome , Rome, Italy
                [3] 3Otolaryngology Unit, San Giovanni Addolorata Hospital , Rome, Italy
                [4] 4Department of Surgical Sciences, University of Turin , Turin, Italy
                [5] 5Department of Surgery and Biomedical Sciences, Section of Otorhinolaryngology, “Santa Maria della Misericordia” University Hospital , Perugia, Italy
                Author notes

                Edited by: P. Ashley Wackym, The State University of New Jersey, United States

                Reviewed by: Franco Trabalzini, University of Florence, Italy; Alessandra Fioretti, European Hospital, Italy

                *Correspondence: Arianna Di Stadio ariannadistadio@ 123456hotmail.com

                This article was submitted to Neuro-Otology, a section of the journal Frontiers in Neurology

                †These authors share last authorship

                Article
                10.3389/fneur.2021.707207
                8373381
                34421805
                8f539437-4139-4bee-89d1-582af66bc15c
                Copyright © 2021 De Luca, Scarpa, Ralli, Tassone, Simone, De Campora, Cassandro and Di Stadio.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 May 2021
                : 28 June 2021
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 49, Pages: 9, Words: 5431
                Categories
                Neurology
                Systematic Review

                Neurology
                covid-19,hearing loss,sars-cov-2,brain inflammation,tinnitus,sudden hearing impairment
                Neurology
                covid-19, hearing loss, sars-cov-2, brain inflammation, tinnitus, sudden hearing impairment

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