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Current Allergy and Asthma Reports
Published in: Current Allergy and Asthma Reports 2/2021

01-02-2021 | Smelling Disorder | Rhinosinusitis (J Mullol, Section Editor)

Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?

Authors: Ming Zeng, De-Yun Wang, Joaquim Mullol, Zheng Liu

Published in: Current Allergy and Asthma Reports | Issue 2/2021

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Abstract

Purpose of Review

Chemosensory dysfunction in the patients with COVID-19 has been reported frequently in the studies from different regions of the world. However, the prevalence of smell and/or taste disorders presents significant ethnic and geographic variability. In addition, the pathogenesis of chemosensory dysfunction remains unclarified.

Recent Findings

This is a narrative review on the recent state of the prevalence, mechanism, and diagnostic and therapeutic strategy of chemosensory dysfunction in COVID-19 patients during the global pandemic. The chemosensory dysfunction was analysis based on recent studies, which either used questionnaires, Likert scales (0–10), or smell tests to estimate the smell and taste dysfunction. The ethnic and geographic difference of the prevalence of smell and/or taste disorders and the potential underlying mechanisms have been discussed. Several suggestions on the diagnosis and treatment of COVID-19 patients with smell and taste disorders were summarized for the physicians.

Summary

This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak.
Literature
1.
Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.PubMedCrossRef
2.
Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study. Clin Infect Dis. 2020;71(15):889–90.PubMedCrossRef
3.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251–61.PubMedPubMedCentralCrossRef
4.
Mullol J, Mariño-Sánchez F, Valls M, Alobid I, Marin C. The sense of smell in chronic rhinosinusitis. J Allergy Clin Immunol. 2020;145(3):773–6.PubMedCrossRef
5.
Yan CH, Faraji F, Prajapati DP, Ostrander BT, DeConde AS. Self-reported olfactory loss associates with outpatient clinical course in COVID-19. Int Forum Allergy Rhinol. 2020;10(7):821–31.PubMedCrossRef
6.
Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020;58(3):299–301.PubMedCrossRef
7.
Soler ZM, Patel ZM, Turner JH, Holbrook EH. A primer on viral-associated olfactory loss in the era of COVID-19. Int Forum Allergy Rhinol. 2020;10(7):814–20.PubMedCrossRef
8.
Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, et al. Position paper on olfactory dysfunction. Rhinology. 2017;0(0):1–30.
9.
Jaume F, Quintó L, Alobid I, Mullol J. Overuse of diagnostic tools and medications in acute rhinosinusitis in Spain: a population-based study (the PROSINUS study). BMJ Open. 2018;8(1).
10.
Izquierdo-Domínguez A, Rojas-Lechuga MJ, Chiesa-Estomba C, Calvo-Henríquez C, Ninchritz-Becerra E, Soriano-Reixach M, et al. Smell and taste dysfunction in COVID-19 is associated with younger age in ambulatory settings: a Multicenter cross-sectional study. J Investig Allergol Clin Immunol. 2020;30(5):346–57.PubMedCrossRef
11.
•• Mullol J, Alobid I, Mariño-Sánchez F, Izquierdo-Domínguez A, Marin C, Klimek L, et al. The loss of smell and taste in the COVID-19 Outbreak: a tale of many countries. Curr Allergy Asthma Rep. 2020;20(10). COMMENT: Summary of the main points of the smell and taste disorders in the COVID-19 worldwide outbreak.
12.
•• Butowt R, von Bartheld CS. Anosmia in COVID-19: Underlying mechanisms and assessment of an olfactory route to brain infection. The Neuroscientist. 2020:1073858420956905 COMMENT: Excellent overview of olfactory dysfunction in COVID-19 from the perspective of neuroscience.
13.
•• Cooper KW, Brann DH, Farruggia MC, Bhutani S, Pellegrino R, Tsukahara T, et al. COVID-19 and the chemical senses: supporting players take center stage. Neuron. 2020;107(2):219–33. COMMENT: Explanation of the underlying mechanisms of chemical senses disorders in COVID-19.PubMedPubMedCentralCrossRef
14.
von Bartheld CS, Hagen MM, Butowt R. Prevalence of chemosensory dysfunction in COVID-19 patients: a systematic review and meta-analysis reveals significant ethnic differences. ACS Chem Neurosci. 2020;11(19):2944–61.CrossRef
15.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6).
16.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China The Lancet. 2020;395(10223):497–506.CrossRef
17.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620–9.PubMedPubMedCentralCrossRef
18.
Patel A, Charani E, Ariyanayagam D, Abdulaal A, Denny SJ, Mughal N, et al. New-onset anosmia and ageusia in adult patients diagnosed with SARS-CoV-2 infection. Clin Microbiol Infect. 2020;26(9):1236–41.PubMedPubMedCentralCrossRef
19.
Paderno A, Schreiber A, Grammatica A, Raffetti E, Tomasoni M, Gualtieri T, et al. Smell and taste alterations in COVID-19: a cross-sectional analysis of different cohorts. Int Forum Allergy Rhinol. 2020;10(8):955–62.PubMedCrossRef
20.
Villarreal IM, Morato M, Martínez-RuizCoello M, Navarro A, Garcia-Chillerón R, Ruiz Á, et al. Olfactory and taste disorders in healthcare workers with COVID-19 infection. Eur Arch Otorhinolaryngol. 2020;1–5.
21.
Rojas-Lechuga MJ, Izquierdo-Domínguez A, Chiesa-Estomba C, Calvo-Henríquez C, Villarreal IM, Cuesta-Chasco G, et al. Chemosensory dysfunction in COVID-19 out-patients. Eur Arch Otorhinolaryngol. 2020.
22.
Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol. 2020;10(7):806–13.PubMedCrossRef
23.
Kempker RR, Kempker JA, Peters M, Rebolledo PA, Carroll K, Toomer L, et al. Loss of smell and taste among healthcare personnel screened for coronavirus 2019. Clin Infect Dis. 2020;ciaa877.
24.
Chiesa-Estomba CM, Lechien JR, Portillo-Mazal P, Martínez F, Cuauro-Sanchez J, Calvo-Henriquez C, et al. Olfactory and gustatory dysfunctions in COVID-19. First reports of Latin-American ethnic patients. Am J Otolaryngol. 2020;41(5):102605.PubMedPubMedCentralCrossRef
25.
Carignan A, Valiquette L, Grenier C, Musonera JB, Nkengurutse D, Marcil-Héguy A, et al. Anosmia and dysgeusia associated with SARS-CoV-2 infection: an age-matched case–control study. Can Med Assoc J. 2020;192(26):E702–E7.CrossRef
26.
Lee DJ, Lockwood J, Das P, Wang R, Grinspun E, Lee JM. Self-reported anosmia and dysgeusia as key symptoms of coronavirus disease 2019. Cjem. 2020;22(5):595–602.PubMedCrossRef
27.
Cho RHW, To ZWH, Yeung ZWC, Tso EYK, Fung KSC, Chau SKY, et al. COVID-19 viral load in the severity of and recovery from olfactory and gustatory dysfunction. Laryngoscope. 2020;130:2680–5.PubMedCrossRef
28.
Liang Y, Xu J, Chu M, Mai J, Lai N, Tang W, et al. Neurosensory dysfunction: a diagnostic marker of early COVID-19. Int J Infect Dis. 2020;98:347–52.PubMedPubMedCentralCrossRef
29.
30.
Lechien JR, Chiesa-Estomba Md CM, Hans S, Barillari Md MR, Jouffe L, Saussez S. Loss of Smell and Taste in 2013 European patients with mild to moderate COVID-19. Ann Intern Med. 2020.
31.
Noh JY, Yoon JG, Seong H, Choi WS, Sohn JW, Cheong HJ, et al. Asymptomatic infection and atypical manifestations of COVID-19: comparison of viral shedding duration. J Inf Secur. 2020.
32.
Lee Y, Min P, Lee S, Kim S-W. Prevalence and duration of acute loss of smell or taste in COVID-19 patients. J Korean Med Sci. 2020;35(18).
33.
Asai N, Sakanashi D, Nakamura A, Kishino T, Kato H, Hagihara M, et al. Clinical manifestations and radiological features by chest computed tomographic findings of a novel coronavirus disease-19 pneumonia among 92 patients in Japan. J Microbiol Immunol Infect. 2020.
34.
Lovato A, Antonini A, de Filippis C. Comment on “The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis”. Otolaryngology–Head and Neck Surgery. 2020;163(4):852.PubMedCrossRef
35.
Meng X, Deng Y, Dai Z, Meng Z. COVID-19 and anosmia: a review based on up-to-date knowledge. Am J Otolaryngol. 2020;41(5).
36.
Agyeman AA, Chin KL, Landersdorfer CB, Liew D, Ofori-Asenso R. Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analysis. Mayo Clin Proc. 2020;95(8):1621–31.PubMedCrossRef
37.
Vaira LA, Deiana G, Fois AG, Pirina P, Madeddu G, De Vito A, et al. Objective evaluation of anosmia and ageusia in COVID-19 patients: single-center experience on 72 cases. Head Neck. 2020;42(6):1252–8.PubMedPubMedCentralCrossRef
38.
Pang KW, Chee J, Subramaniam S, Ng CL. Frequency and clinical utility of olfactory dysfunction in COVID-19: a systematic review and meta-analysis. Curr Allergy Asthma Rep. 2020;20(12).
39.
Li Q, Wu J, Nie J, Zhang L, Hao H, Liu S, et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell. 2020;182(5):1284–94.e9.CrossRef
40.
Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell. 2020;182(4):812–27.e19.CrossRef
41.
42.
43.
Benetti E, Tita R, Spiga O, Ciolfi A, Birolo G, Bruselles A, et al. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. Eur J Hum Genet. 2020.
44.
Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discovery. 2020;6(1).
45.
Strafella C, Caputo V, Termine A, Barati S, Gambardella S, Borgiani P, et al. Analysis of ACE2 genetic variability among populations highlights a possible link with COVID-19-related neurological complications. Genes. 2020;11(7).
46.
47.
Haehner A, Draf J, Dräger S, de With K, Hummel T. Predictive value of sudden olfactory loss in the diagnosis of COVID-19. Orl. 2020;82(4):175–80.PubMedCrossRef
48.
Roland LT, Gurrola JG, Loftus PA, Cheung SW, Chang JL. Smell and taste symptom-based predictive model for COVID-19 diagnosis. Int Forum Allergy Rhinol. 2020;10(7):832–8.PubMedCrossRef
49.
Boudjema S, Finance J, Coulibaly F, Meddeb L, Tissot-Dupont H, Michel M, et al. Olfactory and gustative disorders for the diagnosis of COVID-19. Travel Med Infect Dis. 2020;37:101875.PubMedPubMedCentralCrossRef
50.
Huart C, Philpott C, Konstantinidis I, Altundag A, Trecca EMC, Cassano M, et al. Comparison of COVID-19 and common cold chemosensory dysfunction. Rhinology. 2020.
51.
Hwang CS. Olfactory neuropathy in severe acute respiratory syndrome: report of a case. Acta Neurol Taiwanica. 2006;15(1):26–8.
52.
Malhotra P, Luka A, McWilliams CS, Poeth KG, Schwartz R, Elfekey M, et al. Clinical features of respiratory viral infections among inpatients at a major US tertiary care hospital. South Med J. 2016;109(8):481–6.PubMedCrossRef
53.
Pellegrino R, Walliczek-Dworschak U, Winter G, Hull D, Hummel T. Investigation of chemosensitivity during and after an acute cold. Int Forum Allergy Rhinol. 2017;7(2):185–91.PubMedCrossRef
54.
Tong JY, Wong A, Zhu D, Fastenberg JH, Tham T. The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2020;163(1):3–11.PubMedCrossRef
55.
Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC. COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg. 2020;163(1):132–4.PubMedCrossRef
56.
Eliezer M, Hamel A-L, Houdart E, Herman P, Housset J, Jourdaine C, et al. Loss of smell in COVID-19 patients: MRI data reveals a transient edema of the olfactory clefts. Neurology. 2020;95:e3145–52.PubMedCrossRef
57.
Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26(5):681–7.PubMedPubMedCentralCrossRef
58.
Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020;181(5):1016–35.e19.CrossRef
59.
Butowt R, Bilinska K. SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem Neurosci. 2020;11(9):1200–3.PubMedCrossRef
60.
•• Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science Advances. 2020;6(31). COMMENT: Study suggests that SARS-CoV-2 infection of non-neuronal cell types leads to olfactory dysfunction in patients with COVID-19.
61.
Bryche B, St Albin A, Murri S, Lacôte S, Pulido C, Ar Gouilh M, et al. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun. 2020;89:579–86.PubMedPubMedCentralCrossRef
62.
Jia C, Roman C, Hegg CC. Nickel Sulfate induces location-dependent atrophy of mouse olfactory epithelium: protective and proliferative role of Purinergic receptor activation. Toxicol Sci. 2010;115(2):547–56.PubMedPubMedCentralCrossRef
63.
64.
Gibson G, Hevezi P, Moyer BD, Lu M, Gao N, White E, et al. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes. PLoS One. 2009;4(7):e6395.CrossRef
65.
Kirschenbaum D, Imbach LL, Ulrich S, Rushing EJ, Keller E, Reimann RR, et al. Inflammatory olfactory neuropathy in two patients with COVID-19. The Lancet. 2020;396(10245).
66.
Cazzolla AP, Lovero R, Lo Muzio L, Testa NF, Schirinzi A, Palmieri G, et al. Taste and smell disorders in COVID-19 patients: role of Interleukin-6. ACS Chem Neurosci. 2020;11(17):2774–81.PubMedCrossRef
67.
Yee KK, Li Y, Redding KM, Iwatsuki K, Margolskee RF, Jiang P. Lgr5-EGFP Marks taste bud stem/progenitor cells in posterior tongue. Stem Cells. 2013;31(5):992–1000.PubMedPubMedCentralCrossRef
68.
Barlow LA, Qin Y, Sukumaran SK, Jyotaki M, Redding K, Jiang P, et al. Gli3 is a negative regulator of Tas1r3-expressing taste cells. PLoS Genet. 2018;14(2):e1007058.CrossRef
69.
Cadwell K, Kaufman A, Choo E, Koh A, Dando R. Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLoS Biol. 2018;16(3):e2001959.CrossRef
70.
Meyerhof W, Kim A, Feng P, Ohkuri T, Sauers D, Cohn ZJ, et al. Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease. PLoS One. 2012;7(4):e35588.CrossRef
71.
Cohn ZJ, Kim A, Huang L, Brand J, Wang H. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells. BMC Neurosci. 2010;11(1):72.PubMedPubMedCentralCrossRef
72.
Klimek L, Hagemann J, Alali A, Spielhaupter M, Huppertz T, Hörmann K, et al. Telemedicine allows quantitative measuring of olfactory dysfunction in COVID-19. Allergy. 2020.
73.
Pfaar O, Klimek L, Jutel M, Akdis CA, Bousquet J, Breiteneder H, et al. COVID-19 pandemic: practical considerations on the organization of an allergy clinic – an EAACI/ARIA position paper. Allergy. 2020.
74.
Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, et al. Position paper on olfactory dysfunction. Rhinol Suppl. 2017;54(26):1–30.PubMedCrossRef
75.
Bousquet J, Akdis C, Jutel M, Bachert C, Klimek L, Agache I, et al. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: an ARIA-EAACI statement. Allergy. 2020;75:2440–4.PubMedCrossRef
Metadata
Title
Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?
Authors
Ming Zeng
De-Yun Wang
Joaquim Mullol
Zheng Liu
Publication date
01-02-2021
Publisher
Springer US
Published in
Current Allergy and Asthma Reports / Issue 2/2021
Print ISSN: 1529-7322
Electronic ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-020-00987-5

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