Conductive loss occurs due to impaired nasal airflow and is reversible when the obstruction clears; sensorineural loss implies dysfunction of the OE and can be permanent or have a longer time course to functional recovery. 21:92–96. 2003) and postmortem specimens (Gu et al. Initially, odorants enter the superior aspect of the nasal cavity, which is lined by the olfactory epithelium (OE; see Whitman and Greer 2009). Covid-19 testing. 1989). • In the patients with SARS-CoV, a high level of ACE2 expression was demonstrated in the nasal respiratory epithelium (Bertram et al. At least five cell types exist in this epithelial layer: olfactory sensory neurons (OSNs), sustentacular cells, microvillar cells, duct cells of the olfactory (Bowman’s) glands, and basal cells (van Riel et al. 2020). Online ahead of print. Preliminary data from Fodoulian et al. 2010). Viral URIs classically manifest as rhinorrhea and nasal obstruction, leading to conductive olfactory loss. When healthy volunteers were inoculated with the HCoV-229E strain, patients began to report nasal obstruction and an impaired sense of smell. 1994). The cerebrospinal fluid of this patient was found to have a high SARS-CoV viral load (6884 copies/mL). OSNs are bipolar neurons with axons that form synapses in the olfactory bulb, as well as dendrites that project out into the nasal cavity and are enwrapped by sustentacular cells (Liang 2018). The purpose of this study was to determine if … 2020). All of these viruses contain a viral spike protein (S protein) belonging to a group of class I viral fusion proteins. HCA Lung Biological Network. While SARS-CoV-2 has yet to be detected in the CNS, it is important to consider prolonged anosmia as part of COVID-19 symptomatology given the neuroinvasive potentials of previously studied coronavirus strains. All rights reserved. Int J Environ Res Public Health. Olfactory dysfunction in multiple sclerosis. 2015). Akerlund A, Bende M, Murphy C. 1995. Steroids inhibit this OSN regeneration as seen in murine models of OE injury from intranasal lipopolysaccharide administration (Crisafulli et al. Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM, et al. Based on reviewing anosmia as a result of viral infection, specific mechanisms of anosmia can be postulated. Methods: A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar from 1 June 2020 to 12 June 2020. Interestingly, administering cyclosporine to induce immune suppression during HCoV-OC43 inoculation did not prevent the formation of vacuolating lesions and neuronal death in mice, which suggests that some aspects of neurodegeneration are not immunologically mediated (Jacomy and Talbot 2003). NLM Olfactory disorders can result from viral infections of the OSN and retrograde propagation to the higher-order neurons in the olfactory pathway. 2020). 2004). We aim to review the pathophysiology of anosmia related to viral upper respiratory infections and the prognostic implications. 1990). The rates of permanent anosmia post-COVID-19 infection and impact of viral treatment regimens should be assessed. 20(4):738–750. Epub 2020 Oct 28. Olfactory Cleft Measurements and COVID-19-Related Anosmia. Therefore, this review will be focused on the olfactory system. New data are being uncovered about the identity of cells responsible for viral entry into the olfactory neural system. For permissions, please e-mail: journals.permissions@oup.com, This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, Data-science based analysis of patient subgroup structures suggest effects of rhinitis on all chemosensory perceptions in the upper airways, Accounting For Subjectivity In Experimental Research On Human Olfaction, Odor Canopy: A Method for Comfortable Odorant Delivery in MRI, Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms, Current evidence regarding SARS-CoV-2-related anosmia, Possible mechanisms of anosmia in SARS-CoV-2 patients, www.entuk.org/loss-sense-smell-marker-covid-19-infection, https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model, Receive exclusive offers and updates from Oxford Academic. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, et al. About 72.6% of these patients recovered olfactory function within the first 8 days, which suggests that the majority of anosmia is temporary in nature (Lechien et al. 2002). National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The basal cells (both globose and horizontal types) are pluripotent and can give rise to all subtypes of OE cells (Beites et al. Pellegrino R, Cooper KW, Di Pizio A, Joseph PV, Bhutani S, Parma V. Chem Senses. Coronavirus disease 2019 (COVID-19) is a multiorgan manifestation caused by an infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first discovered in Wuhan, China, in 2019.  |  doi: 10.1111/jnc.15197. Another plausible mechanism of viral entry to the CNS is by direct brain inoculation from epithelial disruption at the blood-brain barrier following hematologic seeding of SARS-CoV-2 from other organs. Delayed Septal Perforation as a Complication of COVID-19: A Case Report. In May 2020 anosmia was recognised as a symptom of covid-195 in light of accumulating evidence, including a meta-analysis which showed a loss of smell in 55% (95% confidence interval 38% to 70%) of patients with covid-19.6 A large online questionnaire based survey found that, in covid-19, loss of smell is usually severe and sudden in onset, but transient in most … COVID-19 is an emerging, rapidly evolving situation. Would you like email updates of new search results? Online ahead of print. 2015; Diodato et al. 2005). Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, et al. BACKGROUND AND PURPOSE: Unique among the acute neurologic manifestations of Severe Acute Respiratory Syndrome coronavirus 2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is chemosensory dysfunction (anosmia or dysgeusia), which can be seen in patients who are otherwise oligosymptomatic or even asymptomatic. With few studies published yet, we can only speculate on the mechanism of anosmia symptoms in SARS-CoV-2 patients. 1998). This would not only result in major ramifications on brain homeostasis but also cause central and peripheral olfactory disturbance (Kabbani and Olds 2020). It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. 2020), again supportive of a conductive mechanism. Nat Commun. It is not yet known if prolonged olfactory disturbance correlates with the degree of symptoms generally. 2020). Although the etiology of MS remains disputed, it is postulated that genetic factors (Ebers and Sadovnick 1994) and viral pathogens, such as HCoV, induce CNS demyelination via chronic infection of oligodendrocytes (Perlman 1998; Arbour et al. 2018; Carotenuto et al. Review of pathological and immunological aspects, Immunopathogenesis of coronavirus infections: implications for SARS, Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain, Spread of a neurotropic murine coronavirus into the CNS via the trigeminal and olfactory nerves, Viral replication in olfactory receptor neurons and entry into the olfactory bulb and brain, Intranasal inoculation with the olfactory bulb line variant of mouse hepatitis virus causes extensive destruction of the olfactory bulb and accelerated turnover of neurons in the olfactory epithelium of mice, The diagnosis of a conductive olfactory loss, A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry, Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs, Aquaporin pathways and mucin secretion of Bowman’s glands might protect the olfactory mucosa, Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection, The neurotropic herpes viruses: herpes simplex and varicella-zoster, Human coronavirus gene expression in the brains of multiple sclerosis patients, SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes, Identification of viruses in patients with postviral olfactory dysfunction, Characteristics of olfactory disorders in relation to major causes of olfactory loss, Olfactory mucosa in herpes simplex encephalitis, Anosmia and ageusia: common findings in COVID-19 patients, The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system, Microglia are required for protection against lethal coronavirus encephalitis in mice, Adult neurogenesis and the olfactory system, 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, Olfactory mucosal findings and clinical course in patients with olfactory disorders following upper respiratory viral infection, Human aminopeptidase N is a receptor for human coronavirus 229E, HCA Lung Biological Network. 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