Olfactory Dysfunction in Patients With Coronavirus Disease 2019: A Review

Guoli Wei, Jialin Gu, Zhancheng Gu, Cheng Du, Xiaofei Huang, Haiyan Xing, Lingchang Li, Aiping Zhang, Xingxing Hu, Jiege Huo, Guoli Wei, Jialin Gu, Zhancheng Gu, Cheng Du, Xiaofei Huang, Haiyan Xing, Lingchang Li, Aiping Zhang, Xingxing Hu, Jiege Huo

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on public-health and economic systems worldwide. Among the several neurological symptoms of patients with COVID-19 reported in clinical practice, olfactory dysfunction (OD) is the most common. OD occurs as the earliest or the only clinical manifestation in some patients. Increasing research attention has focused on OD, which is listed as one of the main diagnostic symptoms of severe acute respiratory syndrome-coronavirus-2 infection. Multiple clinical and basic-science studies on COVID-19-induced OD are underway to clarify the underlying mechanism of action. In this review, we summarize the clinical characteristics, mechanisms, evaluation methods, prognosis, and treatment options of COVID-19-induced OD. In this way, we hope to improve the understanding of COVID-19-induced OD to aid early identification and precise intervention.

Keywords: COVID-19; clinical characteristics; mechanism; olfactory dysfunction; treatment.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Wei, Gu, Gu, Du, Huang, Xing, Li, Zhang, Hu and Huo.

Figures

Figure 1
Figure 1
Potential mechanisms of coronavirus disease 2019 (COVID-19)-induced olfactory dysfunction. (i) COVID-19 directly affects sustentacular (SUS) cells through interactions with the ACE2 receptor, thereby leading to abnormal transmission of odor molecules. (ii) Injury to SUS cells, horizontal basal cells (HBCs) as well as the release of cytokines and proinflammatory factors in the systemic and local nasal epithelium lead to abnormal function of olfactory sensory neurons (OSNs). (iii) Olfactory-bulb vascular pericytes, glial-cell injury, and release of cytokines and proinflammatory factors into the systemic and local brain trigger abnormalities in functions of the olfactory bulb and limbic system of the brain.

References

    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. . 2020 Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. (2020) 382:1708–20. 10.1056/NEJMoa2002032
    1. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. (2021) 19:141–54. 10.1038/s41579-020-00459-7
    1. Zhu J, Ji P, Pang J, Zhong Z, Li H, He C, et al. . Clinical characteristics of 3062 COVID-19 patients: a meta-analysis. J Med Virol. (2020) 92:1902–14. 10.1002/jmv.25884
    1. Fantozzi PJ, Pampena E, Di Vanna D, Pellegrino E, Corbi D, Mammucari S, et al. . Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19. Am J Otolaryngol. (2020) 41:102721. 10.1016/j.amjoto.2020.102721
    1. Wong DKC, Gendeh HS, Thong HK, Lum SG, Gendeh BS, Saim A, et al. . A review of smell and taste dysfunction in COVID-19 patients. Med J Malaysia. (2020) 75:574–81.
    1. Samaranayake LP, Fakhruddin KS, Panduwawala C. Sudden onset, acute loss of taste and smell in coronavirus disease 2019 (COVID-19): a systematic review. Acta Odontol Scand. (2020) 78:467–73. 10.1080/00016357.2020.1787505
    1. Villerabel C, Makinson A, Jaussent A, Picot MC, Negre-Pages L, Rouviere JA, et al. . Diagnostic value of patient-reported and clinically tested olfactory dysfunction in a population screened for COVID-19. JAMA Otolaryngol Head Neck Surg. (2021) 147:271–9. 10.1001/jamaoto.2020.5074
    1. Ugurlu BN, Akdogan O, Yilmaz YA, Yapar D, Aktar Ugurlu G, Yerlikaya HS, et al. . Quantitative evaluation and progress of olfactory dysfunction in COVID-19. Eur Arch Otorhinolaryngol. (2021) 278:2363–9. 10.1007/s00405-020-06516-4
    1. Qiu C, Cui C, Hautefort C, Haehner A, Zhao J, Yao Q, et al. . Olfactory and gustatory dysfunction as an early identifier of COVID-19 in adults and children: an international multicenter study. Otolaryngol Head Neck Surg. (2020) 163:714–21. 10.1177/0194599820934376
    1. Ninchritz-Becerra E, Soriano-Reixach MM, Mayo-Yanez M, Calvo-Henriquez C, Martinez-Ruiz de Apodaca P, Saga-Gutierrez C, et al. . Subjective evaluation of smell and taste dysfunction in patients with mild COVID-19 in Spain. Med Clin. (2021) 156:61–4. 10.1016/j.medcle.2020.08.004
    1. Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C, et al. . alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA. (2020) 323:2089–90. 10.1001/jama.2020.6771
    1. Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, et al. . Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. (2020) 26:1037–40. 10.1038/s41591-020-0916-2
    1. Solomon T. Neurological infection with SARS-CoV-2 - the story so far. Nat Rev Neurol. (2021) 17:65–6. 10.1038/s41582-020-00453-w
    1. Jain A, Kumar L, Kaur J, Baisla T, Goyal P, Pandey AK, et al. . Olfactory and taste dysfunction in coronavirus disease 2019 patients: its prevalence and outcomes. J Laryngol Otol. (2020) 134:1–5. 10.1017/S0022215120002467
    1. Saniasiaya J, Islam MA, Abdullah B. Prevalence of olfactory dysfunction in coronavirus disease 2019 (COVID-19): A meta-analysis of 27,492 patients. Laryngoscope. (2021) 131:865–78. 10.1002/lary.29286
    1. Nouchi A, Chastang J, Miyara M, Lejeune J, Soares A, Ibanez G, et al. . Prevalence of hyposmia and hypogeusia in 390 COVID-19 hospitalized patients and outpatients: a cross-sectional study. Eur J Clin Microbiol Infect Dis. (2021) 40:691–7. 10.1007/s10096-020-04056-7
    1. Speth MM, Singer-Cornelius T, Oberle M, Gengler I, Brockmeier SJ, Sedaghat AR. Olfactory dysfunction and sinonasal symptomatology in COVID-19: prevalence, severity, timing, and associated characteristics. Otolaryngol Head Neck Surg. (2020) 163:114–20. 10.1177/0194599820929185
    1. Brandao Neto D, Fornazieri MA, Dib C, Di Francesco RC, Doty RL, Voegels RL, et al. . Chemosensory dysfunction in COVID-19: prevalences, recovery rates, and clinical associations on a large Brazilian sample. Otolaryngol Head Neck Surg. (2021) 164:512–18. 10.1177/0194599820954825
    1. 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) 77:683–90. 10.1001/jamaneurol.2020.1127
    1. 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) 277:2251–61. 10.1007/s00405-020-05965-1
    1. 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) 10:806–13. 10.1002/alr.22579
    1. Wu D, Wang VY, Chen YH, Ku CH, Wang PC. The prevalence of olfactory and gustatory dysfunction in covid-19 - A systematic review. Auris Nasus Larynx. (2021) S0385-8146(21)00200-5. 10.1016/j.anl.2021.07.007
    1. 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) 95:1621–31. 10.1016/j.mayocp.2020.05.030
    1. Sayin I, Yasar KK, Yazici ZM. Taste and smell impairment in COVID-19: an AAO-HNS anosmia reporting tool-based comparative study. Otolaryngol Head Neck Surg. (2020) 163:473–9. 10.1177/0194599820931820
    1. Aggarwal S, Garcia-Telles N, Aggarwal G, Lavie C, Lippi G, Henry BM. Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): early report from the United States. Diagnosis. (2020) 7:91–6. 10.1515/dx-2020-0046
    1. 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) 42:1252–8. 10.1002/hed.26204
    1. Lechien JR, Chiesa-Estomba CM, Beckers E, Mustin V, Ducarme M, Journe F, et al. . Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients. J Intern Med. (2021) 290:451–61. 10.1111/joim.13209
    1. 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) 11:2944–61. 10.1021/acschemneuro.0c00460
    1. Cheng MY, Hsih WH, Ho MW, Lai YC, Liao WC, Chen CY, et al. . Younger adults with mild-to-moderate COVID-19 exhibited more prevalent olfactory dysfunction in Taiwan. J Microbiol Immunol Infect. (2021) 54:794–800. 10.1016/j.jmii.2021.01.006
    1. Mendonca CV, Mendes Neto JA, Suzuki FA, Orth MS, Machado Neto H, Nacif SR. Olfactory dysfunction in COVID-19: a marker of good prognosis? Braz J Otorhinolaryngol. (2021) S1808-8694(20)30240-8. 10.1016/j.bjorl.2020.12.002
    1. Kim JW, Han SC, Jo HD, Cho SW, Kim JY. Regional and chronological variation of chemosensory dysfunction in COVID-19: a meta-analysis. J Korean Med Sci. (2021) 36:e40. 10.3346/jkms.2021.36.e40
    1. Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL. Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol. (2020) 10:944–50. 10.1002/alr.22587
    1. Vaira LA, Hopkins C, Petrocelli M, Lechien JR, Chiesa-Estomba CM, Salzano G, et al. . Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study. J Laryngol Otol. (2020) 134:703–9. 10.1017/S0022215120001826
    1. Boscolo-Rizzo P, Menegaldo A, Fabbris C, Spinato G, Borsetto D, Vaira LA, et al. . Six-month psychophysical evaluation of olfactory dysfunction in patients with COVID-19. Chem Senses. (2021) 46:bjab006. 10.1093/chemse/bjab006
    1. Vaira LA, Lechien JR, Khalife M, Petrocelli M, Hans S, Distinguin L, et al. . Psychophysical evaluation of the olfactory function: European multicenter Study on 774 COVID-19 patients. Pathogens. (2021) 10:62. 10.3390/pathogens10010062
    1. 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) 163:3–11. 10.1177/0194599820926473
    1. Singer-Cornelius T, Cornelius J, Oberle M, Metternich FU, Brockmeier SJ. Objective gustatory and olfactory dysfunction in COVID-19 patients: a prospective cross-sectional study. Eur Arch Otorhinolaryngol. (2021) 278:3325–32. 10.1007/s00405-020-06590-8
    1. Lee JC, Nallani R, Cass L, Bhalla V, Chiu AG, Villwock JA. A systematic review of the neuropathologic findings of post-viral olfactory dysfunction: implications and novel insight for the COVID-19 pandemic. Am J Rhinol Allergy. (2021) 35:323–33. 10.1177/1945892420957853
    1. von Bartheld CS, Hagen MM, Butowt R. The D614G virus mutation enhances anosmia in COVID-19 patients: evidence from a systematic review and meta-analysis of studies from South Asia. ACS Chem Neurosci. (2021) 12:3535–49. 10.1021/acschemneuro.1c00542
    1. Moein ST, Hashemian SM, Tabarsi P, Doty RL. Prevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID-19 patients. Int Forum Allergy Rhinol. (2020) 10:1127–35. 10.1002/alr.22680
    1. Mishra P, Gowda V, Dixit S, Kaushik M. Prevalence of new onset anosmia in COVID-19 Patients: is the trend different between European and Indian Population? Indian J Otolaryngol Head Neck Surg. (2020) 72:1–4. 10.1007/s12070-020-01986-8
    1. Desiato VM, Levy DA, Byun YJ, Nguyen SA, Soler ZM, Schlosser RJ. The prevalence of olfactory dysfunction in the general population: a systematic review and meta-analysis. Am J Rhinol Allergy. (2021) 35:195–205. 10.1177/1945892420946254
    1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. (2020) 395:507–13. 10.1016/S0140-6736(20)30211-7
    1. Mercante G, Ferreli F, De Virgilio A, Gaino F, Di Bari M, Colombo G, et al. . Prevalence of taste and smell dysfunction in coronavirus disease 2019. JAMA Otolaryngol Head Neck Surg. (2020) 146:723–8. 10.1001/jamaoto.2020.1155
    1. Bagheri SH, Asghari A, Farhadi M, Shamshiri AR, Kabir A, Kamrava SK, et al. . Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran. Med J Islam Repub Iran. (2020) 34:62. 10.1101/2020.03.23.20041889
    1. Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, et al. . Features of anosmia in COVID-19. Med Mal Infect. (2020) 50:436–9. 10.1016/j.medmal.2020.04.006
    1. Gupta V, Banavara Rajanna L, Upadhyay K, Bhatia R, Madhav Reddy N, Malik D, et al. . Olfactory and gustatory dysfunction in COVID-19 patients from northern India: a cross-sectional observational study. Indian J Otolaryngol Head Neck Surg. (2021) 73:1–8. 10.1007/s12070-021-02391-5
    1. Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC. COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg. (2020) 163:132–4. 10.1177/0194599820922992
    1. Yagmur AR, Akbal Cufali S, Aypak A, Koksal M, Gunes YC, Ozcan KM. Correlation of olfactory dysfunction with lung involvement and severity of COVID-19. Ir J Med Sci. (2021) 2021:1–6. 10.1007/s11845-021-02732-x
    1. Goshtasbi K, Pang J, Lehrich BM, Vasudev M, Birkenbeuel JL, Abiri A, et al. . Association between olfactory dysfunction and critical illness and mortality in COVID-19: a meta-analysis. Otolaryngol Head Neck Surg. (2021) 2021:945998211017442. 10.1177/01945998211017442
    1. Tabari A, Golpayegani G, Tabari A, Saedi B, Mahdkhah A, Amali A, et al. . Olfactory dysfunction is associated with more severe clinical course in COVID-19. Indian J Otolaryngol Head Neck Surg. (2021) 2021:1–6. 10.1007/s12070-021-02507-x
    1. Speth MM, Singer-Cornelius T, Oberle M, Gengler I, Brockmeier SJ, Sedaghat AR. Mood, anxiety and olfactory dysfunction in COVID-19: evidence of central nervous system involvement? Laryngoscope. (2020) 130:2520–5. 10.1002/lary.28964
    1. Islek A, Balci MK. Phantosmia with COVID-19 related olfactory dysfunction: report of nine case. Indian J Otolaryngol Head Neck Surg. (2021) 2021:1–3. 10.1007/s12070-021-02505-z
    1. Bhattacharjee AS, Joshi SV, Naik S, Sangle S, Abraham NM. Quantitative assessment of olfactory dysfunction accurately detects asymptomatic COVID-19 carriers. EClinicalMedicine. (2020) 28:100575. 10.1016/j.eclinm.2020.100575
    1. Li J, Wang X, Zhu C, Lin Z, Xiong N. Affected olfaction in COVID-19: re-defining “asymptomatic”. EClinicalMedicine. (2020) 29:100628. 10.1016/j.eclinm.2020.100628
    1. Larremore DB, Toomre D, Parker R. Modeling the effectiveness of olfactory testing to limit SARS-CoV-2 transmission. Nat Commun. (2021) 12:3664. 10.1038/s41467-021-23315-5
    1. Lechien JR, Cabaraux P, Chiesa-Estomba CM, Khalife M, Hans S, Calvo-Henriquez C, et al. . Objective olfactory evaluation of self-reported loss of smell in a case series of 86 COVID-19 patients. Head Neck. (2020) 42:1583–90. 10.1002/hed.26279
    1. Meini S, Suardi LR, Busoni M, Roberts AT, Fortini A. Olfactory and gustatory dysfunctions in 100 patients hospitalized for COVID-19: sex differences and recovery time in real-life. Eur Arch Otorhinolaryngol. (2020) 277:3519–23. 10.1007/s00405-020-06102-8
    1. Cristillo V, Pilotto A, Cotti Piccinelli S, Zoppi N, Bonzi G, Gipponi S, et al. . Age and subtle cognitive impairment are associated with long-term olfactory dysfunction after COVID-19 infection. J Am Geriatr Soc. (2021) 69:2778–80. 10.1111/jgs.17296
    1. Garg S, Kim L, Whitaker M, O'Halloran A, Cummings C, Holstein R, et al. . Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 states, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. (2020) 69:458–64. 10.15585/mmwr.mm6915e3
    1. Husain Q, Kokinakos K, Kuo YH, Zaidi F, Houston S, Shargorodsky J. Characteristics of COVID-19 smell and taste dysfunction in hospitalized patients. Am J Otolaryngol. (2021) 42:103068. 10.1016/j.amjoto.2021.103068
    1. Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc Natl Acad Sci USA. (2020) 117:9241–3. 10.1073/pnas.2004999117
    1. Lv H, Zhang W, Zhu Z, Xiong Q, Xiang R, Wang Y, et al. . Prevalence and recovery time of olfactory and gustatory dysfunction in hospitalized patients with COVID19 in Wuhan, China. Int J Infect Dis. (2020) 100:507–12. 10.1016/j.ijid.2020.09.039
    1. Samimi Ardestani SH, Mohammadi Ardehali M, Rabbani Anari M, Rahmaty B, Erfanian R, Akbari M, et al. . The coronavirus disease 2019: the prevalence, prognosis, and recovery from olfactory dysfunction (OD). Acta Otolaryngol. (2021) 141:171–80. 10.1080/00016489.2020.1836397
    1. Morais AHA, Passos TS, de Lima Vale SH, da Silva Maia JK, Maciel BLL. Obesity and the increased risk for COVID-19: mechanisms and nutritional management. Nutr Res Rev. (2021) 34:209–21. 10.1017/S095442242000027X
    1. Williams FMK, Freidin MB, Mangino M, Couvreur S, Visconti A, Bowyer RCE, et al. . Self-reported symptoms of COVID-19, including symptoms most predictive of SARS-CoV-2 infection, are heritable. Twin Res Hum Genet. (2020) 23:316–21. 10.1017/thg.2020.85
    1. Shahrvini B, Prajapati DP, Said M, Liu J, Srinivas S, Jayaraj S, et al. . Risk factors and characteristics associated with persistent smell loss in coronavirus disease 2019 (COVID-19) patients. Int Forum Allergy Rhinol. (2021) 11:1280–2. 10.1002/alr.22802
    1. Galluzzi F, Rossi V, Bosetti C, Garavello W. Risk factors for olfactory and gustatory dysfunctions in patients with SARS-CoV-2 infection. Neuroepidemiology. (2021) 55:154–61. 10.1159/000514888
    1. Tsivgoulis G, Fragkou PC, Karofylakis E, Paneta M, Papathanasiou K, Palaiodimou L, et al. . Hypothyroidism is associated with prolonged COVID-19-induced anosmia: a case-control study. J Neurol Neurosurg Psychiatry. (2021) 92:911. 10.1136/jnnp-2021-326587
    1. Lu Y, Li X, Geng D, Mei N, Wu PY, Huang CC, et al. . Cerebral micro-structural changes in COVID-19 patients - an MRI-based 3-month follow-up study. EClinicalMedicine. (2020) 25:100484. 10.1016/j.eclinm.2020.100484
    1. 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. 10.1002/lary.29056
    1. Vaira LA, Deiana G, Lechien JR, De Vito A, Cossu A, Dettori M, et al. . Correlations between olfactory psychophysical scores and SARS-CoV-2 viral load in COVID-19 patients. Laryngoscope. (2021) 131:2312–18. 10.1002/lary.29777
    1. Castillo-Lopez IY, Govea-Camacho LH, Rodriguez-Torres IA, Recio-Macias DA, Alobid I, Mullol J. Olfactory dysfunction in a Mexican population outside of COVID-19 pandemic: prevalence and associated factors (the OLFAMEX Study). Curr Allergy Asthma Rep. (2020) 20:78. 10.1007/s11882-020-00975-9
    1. Cavazzana A, Larsson M, Munch M, Hahner A, Hummel T. Postinfectious olfactory loss: a retrospective study on 791 patients. Laryngoscope. (2018) 128:10–15. 10.1002/lary.26606
    1. Wu J, Deng W, Li S, Yang X. Advances in research on ACE2 as a receptor for 2019-nCoV. Cell Mol Life Sci. (2021) 78:531–44. 10.1007/s00018-020-03611-x
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. . SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. (2020) 181:271–80.e8. 10.1016/j.cell.2020.02.052
    1. 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) 181:1016–35.e19.
    1. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. (2004) 203:631–7. 10.1002/path.1570
    1. Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, et al. . Neuropathological features of Covid-19. N Engl J Med. (2020) 383:989–92. 10.1056/NEJMc2019373
    1. Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, et al. . Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. (2021) 24:168–75. 10.1101/2020.06.04.135012
    1. Lempriere S. SARS-CoV-2 detected in olfactory neurons. Nat Rev Neurol. (2021) 17:63. 10.1038/s41582-020-00449-6
    1. 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. Sci Adv. (2020) 6:eabc5801. 10.1126/sciadv.abc5801
    1. Brown LS, Foster CG, Courtney JM, King NE, Howells DW, Sutherland BA. Pericytes and neurovascular function in the healthy and diseased brain. Front Cell Neurosci. (2019) 13:282. 10.3389/fncel.2019.00282
    1. Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, thrombosis, kidney failure, and diabetes: is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. (2020) 9:1417. 10.3390/jcm9051417
    1. Chen R, Wang K, Yu J, Howard D, French L, Chen Z, et al. . The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in the human and mouse brains. Front Neurol. (2020) 11:573095. 10.3389/fneur.2020.573095
    1. Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, et al. . Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. (2020) 92:699–702. 10.1002/jmv.25915
    1. Libby P, Luscher T. COVID-19 is, in the end, an endothelial disease. Eur Heart J. (2020) 41:3038–44. 10.1093/eurheartj/ehaa623
    1. Siddiqi HK, Libby P, Ridker PM. COVID-19 - a vascular disease. Trends Cardiovasc Med. (2021) 31:1–5. 10.1016/j.tcm.2020.10.005
    1. Toor SM, Saleh R, Sasidharan Nair V, Taha RZ, Elkord E. T-cell responses and therapies against SARS-CoV-2 infection. Immunology. (2021) 162:30–43. 10.1111/imm.13262
    1. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodriguez L. SARS-CoV-2 infection: the role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. (2020) 54:62–75. 10.1016/j.cytogfr.2020.06.001
    1. 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) 11:2774–81. 10.1021/acschemneuro.0c00447
    1. Wang S, Le TQ, Kurihara N, Chida J, Cisse Y, Yano M, et al. . Influenza virus-cytokine-protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza. J Infect Dis. (2010) 202:991–1001. 10.1086/656044
    1. Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci. (2001) 2:734–44. 10.1038/35094583
    1. Wolfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Muller MA, et al. . Virological assessment of hospitalized patients with COVID-2019. Nature. (2020) 581:465–9. 10.1038/s41586-020-2196-x
    1. Sungnak W, Huang N, Becavin 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) 26:681–7. 10.1038/s41591-020-0868-6
    1. Chen M, Shen W, Rowan NR, Kulaga H, Hillel A, Ramanathan M, et al. . Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication. Eur Respir J. (2020) 56:2001948. 10.1183/13993003.01948-2020
    1. Fodoulian L, Tuberosa J, Rossier D, Boillat M, Kan C, Pauli V, et al. . SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. iScience. (2020) 23:101839. 10.1016/j.isci.2020.101839
    1. Cecchini MP, Brozzetti L, Cardobi N, Sacchetto L, Gibellini D, Montemezzi S, et al. . Persistent chemosensory dysfunction in a young patient with mild COVID-19 with partial recovery 15 months after the onset. Neurol Sci. (2021) 2021:1–6. 10.1007/s10072-021-05635-y
    1. Suzuki Y, Takeda M, Farbman AI. Supporting cells as phagocytes in the olfactory epithelium after bulbectomy. J Comp Neurol. (1996) 376:509–17. 10.1002/(SICI)1096-9861(19961223)376:4<509::AID-CNE1>;2-5
    1. Vogalis F, Hegg CC, Lucero MT. Ionic conductances in sustentacular cells of the mouse olfactory epithelium. J Physiol. (2005) 562:785–99. 10.1113/jphysiol.2004.079228
    1. Chen M, Reed RR, Lane AP. Chronic inflammation directs an olfactory stem cell functional switch from neuroregeneration to immune defense. Cell Stem Cell. (2019) 25:501–13.e505. 10.1016/j.stem.2019.08.011
    1. Fletcher RB, Das D, Gadye L, Street KN, Baudhuin A, Wagner A, et al. . Deconstructing olfactory stem cell trajectories at single-cell resolution. Cell Stem Cell. (2017) 20:817–30.e8. 10.1016/j.stem.2017.04.003
    1. Schwob JE, Jang W, Holbrook EH, Lin B, Herrick DB, Peterson JN, et al. . Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license. J Comp Neurol. (2017) 525:1034–54. 10.1002/cne.24105
    1. Durante MA, Kurtenbach S, Sargi ZB, Harbour JW, Choi R, Kurtenbach S, et al. . Single-cell analysis of olfactory neurogenesis and differentiation in adult humans. Nat Neurosci. (2020) 23:323–6. 10.1038/s41593-020-0587-9
    1. de Melo GD, Lazarini F, Levallois S, Hautefort C, Michel V, Larrous F, et al. . COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Sci Transl Med. (2021) 13:eabf8396. 10.1126/scitranslmed.abf8396
    1. Lechien JR, Michel J, Radulesco T, Chiesa-Estomba CM, Vaira LA, De Riu G, et al. . Clinical and radiological evaluations of COVID-19 patients with anosmia: preliminary report. Laryngoscope. (2020) 130:2526–31. 10.1002/lary.28993
    1. Mattos JL, Schlosser RJ, Mace JC, Smith TL, Soler ZM. Establishing the minimal clinically important difference for the Questionnaire of Olfactory Disorders. Int Forum Allergy Rhinol. (2018) 8:1041–6. 10.1002/alr.22135
    1. Mattos JL, Edwards C, Schlosser RJ, Hyer M, Mace JC, Smith TL, et al. . A brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. (2019) 9:1144–50. 10.1002/alr.22392
    1. Landis BN, Hummel T, Hugentobler M, Giger R, Lacroix JS. Ratings of overall olfactory function. Chem Senses. (2003) 28:691–4. 10.1093/chemse/bjg061
    1. Bagnasco D, Passalacqua G, Braido F, Tagliabue E, Cosini F, Filauro M, et al. . Quick Olfactory Sniffin' Sticks Test (Q-Sticks) for the detection of smell disorders in COVID-19 patients. World Allergy Organ J. (2021) 14:100497. 10.1016/j.waojou.2020.100497
    1. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. “Sniffin' sticks”: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses. (1997) 22:39–2. 10.1093/chemse/22.1.39
    1. Hura N, Xie DX, Choby GW, Schlosser RJ, Orlov CP, Seal SM, et al. . Treatment of post-viral olfactory dysfunction: an evidence-based review with recommendations. Int Forum Allergy Rhinol. (2020) 10:1065–86. 10.1002/alr.22624
    1. Addison AB, Wong B, Ahmed T, Macchi A, Konstantinidis I, Huart C, et al. . Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction. J Allergy Clin Immunol. (2021) 147:1704–19. 10.1016/j.jaci.2020.12.641
    1. Reiter ER, Coelho DH, Kons ZA, Costanzo RM. Subjective smell and taste changes during the COVID-19 pandemic: Short term recovery. Am J Otolaryngol. (2020) 41:102639. 10.1016/j.amjoto.2020.102639
    1. Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, et al. . Evolution of altered sense of smell or taste in patients with mildly symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. (2020) 146:729–32. 10.1001/jamaoto.2020.1379
    1. Li J, Long X, Zhu C, Wang H, Wang T, Lin Z, et al. . Olfactory dysfunction in recovered coronavirus disease 2019 (COVID-19) patients. Mov Disord. (2020) 35:1100–1. 10.1002/mds.28172
    1. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life–an updated review. Chem Senses. (2014) 39:185–94. 10.1093/chemse/bjt072
    1. Philpott CM, Boak D. The impact of olfactory disorders in the United kingdom. Chem Senses. (2014) 39:711–18. 10.1093/chemse/bju043
    1. Erskine SE, Philpott CM. An unmet need: patients with smell and taste disorders. Clin Otolaryngol. (2020) 45:197–203. 10.1111/coa.13484
    1. Pekala K, Chandra RK, Turner JH. Efficacy of olfactory training in patients with olfactory loss: a systematic review and meta-analysis. Int Forum Allergy Rhinol. (2016) 6:299–307. 10.1002/alr.21669
    1. Sorokowska A, Drechsler E, Karwowski M, Hummel T. Effects of olfactory training: a meta-analysis. Rhinology. (2017) 55:17–26. 10.4193/Rhin16.195
    1. Kattar N, Do TM, Unis GD, Migneron MR, Thomas AJ, McCoul ED. Olfactory Training for postviral olfactory dysfunction: systematic review and meta-analysis. Otolaryngol Head Neck Surg. (2021) 164:244–54. 10.1177/0194599820943550
    1. Hummel T, Rissom K, Reden J, Hahner A, Weidenbecher M, Huttenbrink KB. Effects of olfactory training in patients with olfactory loss. Laryngoscope. (2009) 119:496–9. 10.1002/lary.20101
    1. Altundag A, Cayonu M, Kayabasoglu G, Salihoglu M, Tekeli H, Saglam O, et al. . Modified olfactory training in patients with postinfectious olfactory loss. Laryngoscope. (2015) 125:1763–6. 10.1002/lary.25245
    1. Seo BS, Lee HJ, Mo JH, Lee CH, Rhee CS, Kim JW. Treatment of postviral olfactory loss with glucocorticoids, Ginkgo biloba, and mometasone nasal spray. Arch Otolaryngol Head Neck Surg. (2009) 135:1000–4. 10.1001/archoto.2009.141
    1. Schriever VA, Merkonidis C, Gupta N, Hummel C, Hummel T. Treatment of smell loss with systemic methylprednisolone. Rhinology. (2012) 50:284–9. 10.4193/Rhino11.207
    1. Nguyen TP, Patel ZM. Budesonide irrigation with olfactory training improves outcomes compared with olfactory training alone in patients with olfactory loss. Int Forum Allergy Rhinol. (2018) 8:977–81. 10.1002/alr.22140
    1. Kim DH, Kim SW, Hwang SH, Kim BG, Kang JM, Cho JH, et al. . Prognosis of olfactory dysfunction according to etiology and timing of treatment. Otolaryngol Head Neck Surg. (2017) 156:371–7. 10.1177/0194599816679952
    1. Blomqvist EH, Lundblad L, Bergstedt H, Stjarne P. Placebo-controlled, randomized, double-blind study evaluating the efficacy of fluticasone propionate nasal spray for the treatment of patients with hyposmia/anosmia. Acta Otolaryngol. (2003) 123:862–8. 10.1080/00016480310002140
    1. Heilmann S, Huettenbrink KB, Hummel T. Local and systemic administration of corticosteroids in the treatment of olfactory loss. Am J Rhinol. (2004) 18:29–33. 10.1177/194589240401800107
    1. Yan CH, Overdevest JB, Patel ZM. Therapeutic use of steroids in non-chronic rhinosinusitis olfactory dysfunction: a systematic evidence-based review with recommendations. Int Forum Allergy Rhinol. (2019) 9:165–76. 10.1002/alr.22240
    1. Kanjanaumporn J, Aeumjaturapat S, Snidvongs K, Seresirikachorn K, Chusakul S. Smell and taste dysfunction in patients with SARS-CoV-2 infection: A review of epidemiology, pathogenesis, prognosis, and treatment options. Asian Pac J Allergy Immunol. (2020) 38:69–77. 10.12932/AP-030520-0826
    1. Whitcroft KL, Gunder N, Cuevas M, Andrews P, Menzel S, Haehner A, et al. . Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients. Eur Arch Otorhinolaryngol. (2021) 278:2891–7. 10.1007/s00405-020-06567-7
    1. Chung TW, Zhang H, Wong FK, Sridhar S, Chan KH, Cheng VC, et al. . Neurosensory rehabilitation and olfactory network recovery in Covid-19-related olfactory dysfunction. Brain Sci. (2021) 11:686. 10.3390/brainsci11060686

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren