COVID-19 related olfactory impairment – diagnostics, significance and treatment


Authors: S. Genzor 1;  M. Sova 1,2;  J. Mizera 1;  P. Jakubec 1
Authors‘ workplace: Klinika plicních nemocí a tuberkulózy, LF UP a FN Olomouc 1;  Klinika nemocí plicních a tuberkulózy, LF MU a FN Brno 2
Published in: Cesk Slov Neurol N 2021; 84/117(4): 347-352
Category: Review Article
doi: 10.48095/cccsnn2021347

Overview

Aim: Smell disorders are frequent symptoms of COVID-19 disease. This systematic review covers the pathophysiology, diagnostics, prognostic significance, and treatment of COVID-19 related smell disorders. Methods: The articles were selected in accordance with the PRISMA guidelines. The inclusion criteria were: 1. peer-reviewed publications; 2. studies on human subjects; 3. studies published in English or Czech; and 4. used filters: meta-analysis/systematic review/randomized controlled trial. The exclusion criteria were: 1. abstracts from conferences; 2. commentaries; and 3. inclusion of subjects younger than 18 years. The databases PubMed and Web of Science were searched. Using the search term “anosmia OR smell loss OR smell disorders OR dysosmia OR parosmia AND COVID-19”, 157 papers were selected for analysis, with 109 being ruled out based on the exclusion criteria. The full texts and their references were obtained and studied, and the references meeting the inclusion criteria were also included in this review, leading to a total of 68 papers selected for the review. Results: Approximately 60% of patients with COVID-19 disease present with smell disorders. Most studies agree anosmia appears more frequently in the mild course of the disease. The inflammation and demyelination of the olfactory nerve fibres probably play a key role in the pathogenesis. Damage to the supporting cells of the olfactory epithelium may also play an important role. Olfactory disorder may persist over a varying period of time after the resolution of the acute phase of COVID-19. Olfactory training seems to be beneficial in the treatment. The data regarding the efficacy of topical corticosteroids are inconsistent. No other drugs have yet demonstrated a clinical effect. Conclusion: Loss of smell is a common accompanying symptom in mostly mild forms of COVID-19. Olfactory training seems to be effective in treating this dysfunction. Pharmacotherapy (including local and systemic corticosteroids) has not yet proven effective.

Keywords:

anosmia – olfactory disorders – COVID-19


Sources

1. Smith TD, Bhatnagar KP. Anatomy of the olfactory system. Handb Clin Neurol 2019; 164: 17–28. doi: 10.1016/B978-0-444-63855-7.00002-2.

2. Schafer L, Mehler L, Hahner A et al. Sexual desire after olfactory loss: quantitative and qualitative reports of patients with smell disorders. Physiol Behav 2019; 15 (201): 64–69. doi: 10.1016/j.physbeh.2018.12. 020.

3. Croy I, Hummel T. Olfaction as a marker for depression. J Neurol 2017; 264 (4): 631–638. doi: 10.1007/s00415-016-8227-8.

4. Parma V, Ohla K, Veldhuizen MG et al. More than smell – COVID-19 is associated with severe impairment of smell, taste, and chemesthesis. Chem Senses 2020; 45 (7): 609–622. doi: 10.1093/chemse/bjaa041.

5. Fang J, Xie S, Li N et al. Postoperative complications of endoscopic versus microscopic transsphenoidal pituitary surgery: a meta-analysis. J Coll Physicians Surg Pak 2018; 28 (7): 554–559. doi: 10.29271/jcpsp.2018.07.554.

6. Hwang K, Yeom SH, Hwang SH. Complications of nasal bone fractures. J Craniofac Surg 2017; 28 (3): 803–805. doi: 10.1097/SCS.0000000000003482.

7. Attems J, Walker L, Jellinger KA. Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathol 2014; 127 (4): 459–475. doi: 10.1007/s00401-014-12 61-7.

8. Desiato VM, Levy DA, Byun YJ et al. The prevalence of olfactory dysfunction in the general population: a systematic review and meta-analysis. Am J Rhinol Allergy 2021; 35 (2): 195–205. doi: 10.1177/1945892420946 254.

9. Vodička J, Meloun M, Příhodová L. Brief evaluation of pleasantness of olfactory and trigeminal stimulants. Arch Otolaryngol Head Neck Surg 2010; 136 (9): 901–907. doi: 10.1001/archoto.2010.150.

10. Hummel T, Whitcroft KL, Andrews P et al. Position paper on olfactory dysfunction. Rhinol Suppl 2017; 54 (26): 1–30. doi: 10.4193/Rhino16.248.

11. Hawkes CH DR. The Neurology of olfaction. New York: Cambridge University Press 2009.

12. Martinec Nováková L, Štěpánková H, Vodička J et al. Přínos vyšetření čichu pro dia­gnostiku neurodegenerativních onemocnění. Cesk Slov Neurol N 2015; 78 (5): 517–525.

13. Rocke J, Hopkins C, Philpott C et al. Is loss of sense of smell a dia­gnostic marker in COVID-19: a systematic review and meta-analysis. Clin Otolaryngol 2020; 45 (6): 914–922. doi: 10.1111/coa.13620.

14. Tong JY, Wong A, Zhu D et al. 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. doi: 10.1177/0194599820926473.

15. Lee Y, Min P, Lee S et al. Prevalence and duration of acute loss of smell or taste in COVID-19 patients. J Korean Med Sci 2020; 35 (18): e174. doi: 10.3346/jkms.2020.35.e174.

16. Santos REA, da Silva MG, do Monte Silva MCB et al. Onset and duration of symptoms of loss of smell/taste in patients with COVID-19: a systematic review. Am J Otolaryngol 2021; 42 (2): 102889. doi: 10.1016/j.amjoto.2020.102889.

17. Moher D, Liberati A, Tetzlaff J et al. Methods of systematic reviews and meta-analysis preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62 (10): 1006–1012. doi: 10.1016/j.jclinepi.2009.06.005.

18. Finsterer J, Stollberger C. Causes of hypogeusia/hyposmia in SARS-CoV2 infected patients. J Med Virol 2020; 92 (10): 1793–1794. doi: 10.1002/jmv.25903.

19. Hopkins C, Lechien JR, Saussez S. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanism of olfactory dysfunction in COVID-19 and its association with enhanced survival. Med Hypotheses 2021; 146: 110406. doi: 10.1016/ j.mehy.2020.110406.

20. Bryche B, St Albin A, Murri S 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: 579–586. doi: 10.1016/j.bbi.2020.06.032.

21. Mao L, Huijuan J, Wang M et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77 (6): 683–690. doi: 10.1001/jamaneurol.2020.1127.

22. Pavlidis P, Cámara RJA, Kekes G et al. Bilateral taste disorders in patients with Ramsay Hunt syndrome and Bell palsy. Ann Neurol 2018; 83 (4): 807–815. doi: 10.1002/ana.25210.

23. Cheng JL, Huang C, Zhang GJ et al. Epidemiological characteristics of novel coronavirus pneumonia in Henan. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43 (4): 327–331. doi: 10.3760/cma.j.cn112147-20200222-00148.

24. Naeini AS, Karimi-Galougahi M, Raad N et al. Paranasal sinuses computed tomography findings in anosmia of COVID-19. Am J Otolaryngol 2020; 41 (6): 102636. doi: 10.1016/j.amjoto.2020.102636.

25. Li X, Zhang C, Liu L et al. Existing bitter medicines for fighting 2019-nCoV-associated infectious diseases. FASEB J 2020; 34 (5): 6008–6016. doi: 10.1096/fj.202000502.

26. Hansen MP, Scott AM, McCullough A et al. Adverse events in people taking macrolide antibio­tics versus placebo for any indication. Cochrane Database Syst Rev 2019; 1 (1): Cd011825. doi: 10.1002/14651858.CD011825.pub2.

27. Mahalakshmi AM, Ray B, Tuladhar S et al. Does COVID-19 contribute to development of neurological disease? Immun Inflamm Dis 2021; 9 (1): 48–58. doi: 10.1002/iid3.387.

28. ElBini Dhouib I. Does coronaviruses induce neurodegenerative diseases? A systematic review on the neurotropism and neuroinvasion of SARS-CoV-2. Drug Discov Ther 2021; 14 (6): 262–272. doi: 10.5582/ddt.2020.03 106.

29. Henkin RI, Potolicchio SJ, Levy LM. Olfactory hallucinations without clinical motor activity: a comparison of unirhinal with birhinal phantosmia. Brain Sci 2013; 3 (4): 1483–1553. doi: 10.3390/brainsci3041483.

30. Mattos JL, Edwards C, Schlosser RJ et al. A brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis. Int Forum Al- lergy Rhinol 2019; 9 (10): 1144–1150. doi: 10.1002/alr.22 392.

31. Hummel T, Kobal G, Gudziol H et al. Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3000 subjects. Eur Arch Otorhinolaryngol 2007; 264 (3): 237–243. doi: 10.1007/s00405-006-0173-0.

32. Vodička J, Pecková L, Kopal A et al. Vyšetření čichu u neurologických onemocnění pomocí Testu parfémovaných fixů. Cesk Slov Neurol N 2010; 73 (1): 45–50.

33. Brothánková P, Vodicka J. Normální hodnoty Nového testu libosti pachů u zdravé populace. Cesk Slov Neurol N 2010; 78 (1): 78–82.

34. Doty RL, Shaman P, Kimmelman CP et al. University of Pennsylvania Smell identification test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 1984; 94 (2 Pt 1): 176–178. doi: 10.1288/00005537-198402000-00004.

35. Cain WS, Gent JF, Goodspeed RB et al. Evaluation of olfactory dysfunction in the Connecticut Chemo­sensory Clinical Research Center. Laryngoscope 1988; 98 (1): 83–88. doi: 10.1288/00005537-198801000-00017.

36. Brattoli M, de Gennaro G, de Pinto V et al. Odour detection methods: olfactometry and chemical sensors. Sensors (Basel) 2011; 11 (5): 5290–5322. doi: 10.3390/s110505290.

37. Hornuss D, Lange B, Schröter N et al. Anosmia in COVID-19 patients. Clin Microbio­l Infect 2020; 26 (10): 1426–1427. doi: 10.1016/j.cmi.2020.05.017.

38. Lechien JR, Chiesa-Estomba CM, De Siati DR 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): 2251–2261. doi: 10.1007/s00405-020-05965-1.

39. Le Bon SD, Pisarski N, Verbeke J et al. Psychophysical evaluation of chemosensory functions 5 weeks after olfactory loss due to COVID-19: a prospective cohort study on 72 patients. Eur Arch Otorhinolaryngol 2021; 278 (1): 101–108. doi: 10.1007/s00405-020-06267-2.

40. Otte MS, Eckel HNC, Poluschkin L et al. Olfactory dysfunction in patients after recovering from COVID-19. Acta Otolaryngol 2020; 140 (12): 1032–1035. doi: 10.1080/00016489.2020.1811999.

41. Altin F, Cingi C, Uzun T et al. Olfactory and gustatory abnormalities in COVID-19 cases. Eur Arch Otorhinolaryngol 2020; 277 (10): 2775–2781. doi: 10.1007/s00405-020-06155-9.

42. Iannuzzi L, Salzo AE, Angarano G et al. Gaining back what is lost: recovering the sense of smell in mild to moderate patients after COVID-19. Chem Senses 2020; 45 (9): 875–881. doi: 10.1093/chemse/bjaa066.

43. Gözen ED, Aliyeva C, Tevetoğlu F et al. Evaluation of olfactory function with objective tests in COVID-19-positive patients: a cross-sectional study. Ear Nose Throat J 2021; 100 (2_suppl): 169S–173S. doi: 10.1177/0145561320975510.

44. Vaira LA, Salzano G, Petrocelli M et al. Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine. Head Neck 2020; 42 (7): 1570–1576. doi: 10.1002/hed.26228.

45. Moein ST, Hashemian SMR, Mansourafshar B et al. Smell dysfunction: a bio­marker for COVID-19. Int Forum Allergy Rhinol 2020; 10 (8): 944–950. doi: 10.1002/alr.22587.

46. Lima MA, Silva MTT, Oliveira RV et al. Smell dysfunction in COVID-19 patients: more than a yes-no question. J Neurol Sci 2020; 418: 117107. doi: 10.1016/j.jns.2020.117107.

47. Bhattacharjee AS, Joshi SV, Naik S et al. Quantitative assessment of olfactory dysfunction accurately detects asymptomatic COVID-19 carriers. E Clinical Medi- cine 2020; 28: 100575. doi: 10.1016/j.eclinm.2020.100575.

48. Li J, Long X, Zhu C et al. Olfactory dysfunction in recovered coronavirus disease 2019 (COVID-19) patients. Mov Disord 2020; 35 (7): 1100–1101. doi: 10.1002/mds. 28172.

49. Hopkins C, Alanin M, Philpott C et al. Management of new onset loss of sense of smell during the COVID-19 pandemic – BRS Consensus Guidelines. Clin Otolaryngol 2021; 46 (1): 16–22. doi: 10.1111/coa.13636.

50. Han P, Zang Y, Akshita J et al. Magnetic reso- nance imaging of human olfactory dysfunction. Brain Topogr 2019; 32 (6): 987–997. doi: 10.1007/s10548-019-00729-5.

51. Politi LS, Salsano E, Grimaldi M. Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurology 2020; 77 (8): 1028–1029. doi: 10.1001/jamaneurol.2020.2125.

52. Aziz M, Goyal H, Haghbin H et al. The association of “Loss of Smell” to COVID-19: a systematic review and meta-analysis. Am J Med Sci 2021; 361 (2): 216–225. doi: 10.1016/j.amjms.2020.09.017.

53. Sanli DET, Altundag A, Kandemirli SG et al. Relationship between disease severity and serum IL-6 levels in COVID-19 anosmia. Am J Otolaryngol 2021; 42 (1): 102796. doi: 10.1016/j.amjoto.2020.102796.

54. Chiesa-Estomba CM, Lechien JR, Radulesco T et al. Patterns of smell recovery in 751 patients affected by the COVID-19 outbreak. Eur J Neurol 2020; 27 (11): 2318–2321. doi: 10.1111/ene.14440.

55. Lechien JR, Chiesa-Estomba CM, De Siati DR 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): 2251–2261. doi: 10.1007/s00405-020-05965-1.

56. Kaye R, Chang CWD, Kazahaya K et al. COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg 2020; 163 (1): 132–134. doi: 10.1177/01 94599820922992.

57. Hopkins C, Surda P, Whitehead E et al. Early recovery following new onset anosmia during the COVID-19 pandemic – an observational cohort study. J Otolaryngol Head Neck Surg 2020; 49 (1): 26. doi: 10.1186/s40463-020-00423-8.

58. Lee Y, Min P, Lee S et al. Prevalence and duration of acute loss of smell or taste in COVID-19 patients. J Korean Med Sci 2020; 35 (18): e174. doi: 10.3346/jkms.2020.35.e174.

59. Klopfenstein T, Kadiane-Oussou NJ, Toko L et al. Features of anosmia in COVID-19. Med Mal Infect 2020; 50 (5): 436–439. doi: 10.1016/j.medmal.2020.04.006.

60. Agyeman AA, Chin KL, Landersdorfer CB et al. Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analyzis. Mayo Clin Proc 2020; 95 (8): 1621–1631. doi: 10.1016/j.mayocp.2020.05.030.

61. Kattar N, Do TM, Unis GD et al. Olfactory training for postviral olfactory dysfunction: systematic review and meta-analysis. Otolaryngol Head Neck Surg 2021; 164 (2): 244–254. doi: 10.1177/0194599820943550.

62. Konstantinidis I, Tsakiropoulou E, Bekiaridou P et al. Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction. Laryngoscope 2013; 123 (12): E85–90. doi: 10.1002/lary.24390.

63. Liu DT, Sabha M, Damm M et al. Parosmia is associated with relevant olfactory recovery after olfactory training. Laryngoscope 2021; 131: 618–623. doi: 10.1002/lary.29277.

64. Saltagi MZ, Rabbani CC, Ting JY et al. Management of long-lasting phantosmia: a systematic review. Int Forum Allergy Rhinol 2018; 8 (7): 790–796. doi: 10.1002/alr.22108.

65. Harless L, Liang J. Pharmacologic treatment for postviral olfactory dysfunction: a systematic review. Int Forum Allergy Rhinol 2016; 6 (7): 760–767. doi: 10.1002/alr.21727.

66. Scangas GA, Bleier BS. Anosmia: differential dia­g­nosis, evaluation, and management. Am J Rhinol Allergy 2017; 31 (1): 3–7. doi: 10.2500/ajra.2017.31.4403.

67. Abdelalim AA, Mohamady AA, Elsayed RA et al. Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: a randomized controlled trial. Am J Otolaryngol 2021; 42 (2): 102884. doi: 10.1016/j.amjoto.2020.102884.

68. Kirtsreesakul V, Wongsritrang K, Ruttanaphol S. Does oral prednisolone increase the efficacy of subsequent nasal steroids in treating nasal polyposis? Am J Rhinol Allergy 2012; 26 (6): 455–462. doi: 10.2500/ajra.2012.26.3820.

69. Huart C, Philpott CM, Altundag A et al. Systemic corticosteroids in coronavirus disease 2019 (COVID-19) -related smell dysfunction: an international view. Int Forum Allergy Rhinol 2021; 11 (7): 1041–1046. doi: 10.1002/alr.22788.

Labels
Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 4

2021 Issue 4

Most read in this issue
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account