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Editorial

The Trajectories of Olfactory Dysfunction from the First to the Omicron Wave: Are We Getting over it?

by
Luigi Angelo Vaira
1,2,*,
Jérome R. Lechien
3,4,
Giacomo De Riu
1 and
Sven Saussez
3
1
Maxillofacial Surgery Operative Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
2
Biomedical Science Department, PhD School of Biomedical Science, University of Sassari, 07100 Sassari, Italy
3
Department of Human and Experimental Oncology, Faculty of Medicine UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), B7000 Mons, Belgium
4
Department of Otolaryngology-Head Neck Surgery, Elsan Polyclinic of Poitiers, 86000 Poitiers, France
*
Author to whom correspondence should be addressed.
Pathogens 2023, 12(1), 10; https://doi.org/10.3390/pathogens12010010
Submission received: 17 December 2022 / Accepted: 20 December 2022 / Published: 21 December 2022
Versions Notes
It has now been two years since the publication in Pathogens of our European multicenter study on the prevalence of olfactory dysfunctions (OD) during COVID-19 [1]. To date, with 774 patients, this is the largest psychophysical study ever published. The study provided a clear picture of the burden of OD during SARS-CoV-2 infection affecting more than 60% of patients during the first two pandemic waves. These data have been confirmed by numerous other authors around the world [2,3,4,5,6].
It was found was that 5 to 40% of these patients developed persistent OD which is now recognized as one of the most frequent symptoms of long-COVID-19 [7,8,9,10,11,12,13]. A severe and persistent reduction in smell has deleterious effects on the quality of life of patients who are propelled towards social isolation and depression [14,15,16] and exposed to environmental hazards. For this reason, researchers’ efforts are now turning to finding risk factors for the development of persistent OD [17,18,19,20,21,22,23,24] and numerous therapeutic trials are underway around the world [25,26,27,28,29,30,31,32].
Recently, some good news has come from the clinical data of patients infected with the Omicron variant which now represents almost all cases. In these patients, the prevalence of OD during infection markedly decreased compared to the previous variants, ranging between 1 and 34% [33,34,35]. Curiously, the Omicron variant has been shown to contain the D614G mutation which has been related to SARS-CoV-2’s ability to induce OD [36]. It is possible that the lower prevalence of OD is at least in part related to a more organized and effective IgA-mediated immune response of the olfactory epithelium of immunized subjects [37]. However, this is certainly not the only reason since, during the previous pandemic waves, OD proved to be a frequent clinical finding even in vaccinated individuals [38] and reinfections [39]. It is therefore probable that factors related to the virus are also implicated: lower pathogenicity [40,41], lower ability to enter cells of the olfactory epithelium through ACE-2 receptors [42,43], lower solubility in nasal mucus [44].
However, there are still no studies with long-term follow-up data to evidence whether this reduced prevalence corresponds to a lower rate of persistent OD. From the first 6 months of collected data, currently being published, the rate of persistent OD in Omicron patients is low and does not show significant differences compared to the general population. Good news that may be a light at the end of the tunnel for those who have found themselves overwhelmed by patients with persistent OD.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Vaira, L.A.; Lechien, J.R.; Khalife, M.; Petrocelli, M.; Hans, S.; Distinguin, L.; Salzano, G.; Cucurullo, M.; Doneddu, P.; Salzano, F.A.; et al. Psychophysical evaluation of the olfactory function: European multicenter study on 774 COVID-19 patients. Pathogens 2021, 10, 62. [Google Scholar] [CrossRef] [PubMed]
  2. Saniasiaya, J.; Islam, M.A.; Abdullah, B. Prevalence of olfactory dysfunction in coronavirus disease 2019 (COVID-19): A meta-analysis of 27,492 patients. Laryngoscope 2021, 131, 865–878. [Google Scholar] [CrossRef]
  3. Haehner, A.; Marquardt, B.; Kardashi, R.; de With, K.; Robler, S.; Landis, B.N.; Welge-Luessen, A.; Hummel, T. SARS-CoV-2 leads to significantly more severe olfactory loss than other seasonal cold viruses. Life 2022, 12, 461. [Google Scholar] [CrossRef]
  4. Lechien, J.R.; Ducarme, M.; Place, S.; Chiesa-Estomba, C.M.; Khalife, M.; De Riu, G.; Vaira, L.A.; de Terwangne, C.; Machayekhi, S.; Marchant, A.; et al. Objective olfactory findings in hospitalized severe COVID-19 patients. Pathogens 2020, 9, 627. [Google Scholar] [CrossRef] [PubMed]
  5. Lechien, J.R.; Chiesa-Estomba, C.M.; Vaira, L.A.; Cammaroto, G.; De Riu, G.; Chekkoury-Idrissi, Y.; Circiu, M.; Distinguin, L.; Journe, F.; de Terwangne, C.; et al. Epidemiological, otolaryngological, olfactory and gustatory outcomes according to the severity of COVID-19: A study of 2579 patients. Eur. Arch. Otorhinolaryngol. 2021, 278, 2851–2859. [Google Scholar] [CrossRef] [PubMed]
  6. Borsetto, D.; Hopkins, C.; Philips, V.; Obholzer, R.; Tirelli, G.; Polesel, J.; Boscolo-Rizzo, P. Self-reported alteration of sense of smell or taste in patients with COVID-19: A systematic review and meta-analysis on 3563 patients. Rhinology 2020, 58, 430–436. [Google Scholar] [CrossRef]
  7. Riestra-Ayora, J.; Yanes-Diaz, J.; Esteban-Sanchez, J.; Vuduva, C.; Molina-Quiros, C.; Larran-Jimenez, A.; Martin-Sanz, E. Long-term follow-up of olfactory and gustatory dysfunction in COVID-19: 6 months case-control study in health workers. Eur. Arch. Otorhinolaryngol. 2021, 278, 4831–4837. [Google Scholar] [CrossRef]
  8. Vaira, L.A.; Salzano, G.; Le Bon, S.; Maglio, A.; Petrocelli, M.; Steffens, Y.; Ligas, E.; Maglitto, F.; Lechien, J.R.; Saussez, S.; et al. Prevalence of persistent olfactory disorders in patients with COVID-19: A psychophysical case-control study with 1-year follow-up. Otolaryngol. Head Neck Surg. 2021, 167, 183–186. [Google Scholar] [CrossRef]
  9. Boscolo-Rizzo, P.; Guida, F.; Polesel, J.; Marcuzzo, A.V.; Antonucci, P.; Capriotti, V.; Sacchet, E.; Cragnolini, F.; D’Alessandro, A.; Zanelli, E.; et al. Self-reported smell and taste recovery in coronavirus disease 2019 patients: A one-year prospective study. Eur. Arch. Otorhinolaryngol. 2021, 279, 515–520. [Google Scholar] [CrossRef]
  10. Boscolo-Rizzo, P.; Hummel, T.; Hopkins, C.; Dibattista, M.; Menini, A.; Spinato, G.; Fabbris, C.; Emanuelli, E.; D’Alessandro, A.; Marzolino, R.; et al. High prevalence of long-term olfactory, gustatory, and chemesthesis dysfunction in post-COVID-19 patients: A matched case-control study with one-year follow-up using a comprehensive psychophysical evaluation. Rhinology 2021, 59, 517–527. [Google Scholar] [CrossRef]
  11. Lechien, J.R.; Vaira, L.A.; Saussez, S. Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study. J. Intern. Med. 2022, 293, 82–90. [Google Scholar] [CrossRef] [PubMed]
  12. Boscolo-Rizzo, P.; Fabbris, C.; Polesel, J.; Emanuelli, E.; Tirelli, G.; Spinato, G.; Hopkins, C. Two-year prevalence and recovery rate of altered sense of smell and taste in patients with mildly symptomatic COVID-19. JAMA Otolaryngol. Head Neck Surg. 2022, 148, 889–891. [Google Scholar] [CrossRef] [PubMed]
  13. Tan, B.K.J.; Han, R.; Zhao, J.J.; Tan, N.K.W.; Quah, E.S.H.; Tan, C.J.; Chan, Y.H.; Teo, N.W.Y.; Charn, T.C.; See, A.; et al. Prognosis and persistence of smell and taste dysfunction in patients with covid-19: Meta-analysis with parametric cure modelling of recovery curves. BMJ 2022, 378, e069503. [Google Scholar] [CrossRef] [PubMed]
  14. Boesveldt, S.; Parma, V. The importance of the olfactory system in human well-being, through nutrition and social behavior. Cell Tissue Res. 2021, 383, 559–567. [Google Scholar] [CrossRef]
  15. Saniasiaya, J.; Prepageran, N. Impact of olfactory dysfunction on quality of life in coronavirus disease 2019 patients: A systematic review. J. Laryngol. Otol. 2021, 135, 947–952. [Google Scholar] [CrossRef]
  16. Vaira, L.A.; Gessa, C.; Deiana, G.; Salzano, G.; Maglitto, F.; Lechien, J.R.; Saussez, S.; Piombino, P.; Biglio, A.; Biglioli, F.; et al. The effects of persistent olfactory and gustatory dysfunctions on quality of life in long-COVID-19 patients. Life 2022, 12, 141. [Google Scholar] [CrossRef]
  17. Vaira, L.A.; Deiana, G.; Lechien, J.R.; De Vito, A.; Cossu, A.; Dettori, M.; Del Rio, A.; Saussez, S.; Madeddu, G.; Babudieri, S.; et al. Correlations between olfactory psychophysical scores and SARS-CoV-2 viral load in COVID-19 patients. Laryngoscope 2021, 131, 2312–2318. [Google Scholar] [CrossRef]
  18. Callejon-Leblic, M.A.; Martin-Jimenez, D.I.; Moreno-Luna, R.; Palacios-Garcia, J.M.; Alvarez-Cendrero, M.; Vizcarra-Melgar, J.A.; Fernandez-Velez, C.; Reyes-Tejero, I.M.; Maza-Solano, J.; Gonzalez-Garcia, J.; et al. Analysis of prevalence and predictive factors of long-lasting olfactory and gustatory dysfunction in COVID-19 patients. Life 2022, 12, 1256. [Google Scholar] [CrossRef]
  19. Tipirdamaz, C.; Zayet, S.; Osman, M.; Mercier, J.; Bouvier, E.; Gendrin, V.; Bouiller, K.; Lepiller, Q.; Toko, L.; Pierron, A.; et al. Asthma and cacosmia could be predictive factors of olfactory dysfunction persistence 9 months after SARS-CoV-2 infection: The ANOSVID study. Life 2022, 12, 929. [Google Scholar] [CrossRef]
  20. Vaira, L.A.; De Vito, A.; Deiana, G.; Pes, C.; Giovanditto, F.; Fiore, V.; Lechien, J.R.; Saussez, S.; Policicchio, D.; Boccaletti, R.; et al. Systemic inflammatory markers and psychophysical olfactory scores in coronavirus disease 2019 patients: Is there any correlation? J. Laryngol. Otol. 2021, 135, 723–728. [Google Scholar] [CrossRef]
  21. Vaira, L.A.; De Vito, A.; Deiana, G.; Pes, C.; Giovanditto, F.; Fiore, V.; Lechien, J.R.; Le Bon, S.-D.; Saussez, S.; Madeddu, G.; et al. Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: A preliminary study. Eur. Arch. Otorhinolaryngol. 2022, 279, 811–816. [Google Scholar] [CrossRef] [PubMed]
  22. Amadu, A.M.; Vaira, L.A.; Lechien, J.R.; Scaglione, M.; Saba, L.; Lampus, M.L.; Profili, S.G.; Le Bon, S.-D.; Salzano, G.; Maglitto, F.; et al. Analysis of the correlations between the severity of lung involvement and olfactory and psychophysical scores in coronavirus disease 2019 (COVID-19) patients. Int. Forum Allergy Rhinol. 2022, 12, 103–107. [Google Scholar] [CrossRef] [PubMed]
  23. Paderno, A.; Schreiber, A.; Grammatica, A.; Raffetti, E.; Tomasoni, M.; Gualtieri, T.; Taboni, S.; Zorzi, S.; Lombardi, D.; Deganello, A.; et al. Smell and taste alterations in COVID-19: A cross-sectional analysis of different cohorts. Int. Forum Allergy Rhinol. 2020, 10, 955–962. [Google Scholar] [CrossRef]
  24. Speth, M.M.; Singer-Cornelius, T.; Oberle, M.; Gengler, I.; Brockmeier, S.J.; Sedaghat, A.R. Olfactory dysfunction and sinonasal symptomatology in COVID-10: Prevalence, severity, timing, and associated characteristics. Otolaryngol. Head Neck Surg. 2020, 163, 114–120. [Google Scholar] [CrossRef] [PubMed]
  25. Saussez, S.; Sharma, S.; Thiriard, A.; Olislagers, V.; Vu Duc, I.; Le Bon, S.D.; Khalife, M.; Hans, S.; De Riu, G.; Hopkins, C.; et al. Predictive factors of smell recovery in a clinical series of 288 coronavirus disease 2019 patients with olfactory dysfunction. Eur. J. Neurol. 2021, 28, 3702–3711. [Google Scholar] [CrossRef] [PubMed]
  26. Hopkins, C.; Alanin, M.; Philpott, C.; Harries, P.; Withcroft, K.; Qureish, A.; Anari, S.; Ramakrishnan, Y.; Sama, A.; Davies, E.; et al. Management of new onset loss of sense of smell during the COVID-19 pandemic-BRS consensus guidelines. Clin. Otolaryngol. 2021, 46, 16–22. [Google Scholar] [CrossRef] [PubMed]
  27. Vaira, L.A.; Hopkins, C.; Petrocelli, M.; Lechien, J.R.; Cutrupi, S.; Salzano, G.; Chiesa-Estomba, C.M.; Saussez, S.; De Riu, G. Efficacy of corticosteroid therapy in the treatment of long-lasting olfactory disorders in COVID-19 patients. Rhinology 2021, 59, 21–25. [Google Scholar] [CrossRef]
  28. Whitcroft, K.L.; Hummel, T. Olfactory dysfunction in COVID-19: Diagnosis and management. JAMA 2020, 323, 2512–2514. [Google Scholar] [CrossRef]
  29. Saussez, S.; Vaira, L.A.; Chiesa-Estomba, C.M.; Bon, S.L.; Horoi, M.; Deiana, G.; Petrocelli, M.; Boelpaep, P.; Salzano, G.; Khalife, M.; et al. Short-term efficacy and safety of oral and nasal corticosteroids in COVID-19 patients with olfactory dysfunction: A European multicenter study. Pathogens 2021, 10, 698. [Google Scholar] [CrossRef]
  30. Lechien, J.R.; Vaira, L.A.; Saussez, S. Effectiveness of olfactory training in COVID-19 patients with olfactory dysfunction: A prospective study. Eur. Arch. Otolaryngol. 2022. [Google Scholar] [CrossRef]
  31. Di Stadio, A.; Ascanio, L.; Vaira, L.A.; Cantone, E.; De Luca, P.; Cingolani, C.; Motta, G.; De Riu, G.; Vitelli, F.; Spriano, G.; et al. Ultramicronized palmitoylethanolamide and luteolin supplement combined with olfactory training to treat post-COVID-19 olfactory impairment: A multicenter double-blinded randomized placebo-controlled clinical trial. Curr. Neuropharmacol. 2022, 20, 2001–2012. [Google Scholar] [CrossRef] [PubMed]
  32. Hintschich, C.A.; Dietz, M.; Haehner, A.; Hummel, T. Topical administration of mometasone is no helpful in post-COVID-19 olfactory dysfunction. Life 2022, 12, 1483. [Google Scholar] [CrossRef] [PubMed]
  33. Boscolo-Rizzo, P.; Tirelli, G.; Meloni, P.; Hopkins, C.; Madeddu, G.; De Vito, A.; Gardenal, N.; Valentinotti, R.; Tofanelli, M.; Borsetto, D.; et al. Coronavirus disease 2019 (COVID-19)-related smell and taste impairment with widespread diffusion of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Omicron variant. Int Forum Allergy Rhinol 2022, 12, 1273–1281. [Google Scholar] [CrossRef] [PubMed]
  34. Vaira, L.A.; Lechien, J.R.; Deiana, G.; Salzano, G.; Maglitto, F.; Piombino, P.; Mazzatenta, A.; Boscolo-rizzo, P.; Hopkins, C.; De Riu, G. Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: A psychophysical case-control study. Rhinology 2022. [Google Scholar] [CrossRef] [PubMed]
  35. Cardoso, C.C.; Rossi, A.D.; Galliez, R.M.; Faffe, D.S.; Tanuri, A.; Castineiras, T.M.P.P. Olfactory dysfunction in patients with mild COVID-19 during gamma, delta and omicron waves in Rio de Janeiro, Brazil. JAMA 2022, 328, 582–583. [Google Scholar] [CrossRef] [PubMed]
  36. von Bartheld, C.S.; Mathew, D.; Butowt, R. New study on prevalence of anosmia in COVID-19 implicates the D614G virus mutation as a major contributing factor to chemosensory dysfunction. Eur. Arch. Otorhinolaryngol. 2021, 278, 3593–3594. [Google Scholar] [CrossRef]
  37. Sheikh-Mohamed, S.; Isho, B.; Chao, G.Y.C.; Zuo, M.; Cohen, C.; Lustig, Y.; Nahass, G.R.; Salomon-Shulman, R.E.; Blacker, G.; Fazel-Zarandi, M.; et al. Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection. Mucosal Immunol. 2022, 15, 799–808. [Google Scholar] [CrossRef]
  38. Vaira, L.A.; De Vito, A.; Lechien, J.R.; Chiesa-Estomba, C.M.; Mayo-Yanez, M.; Calvo-Henriquez, C.; Saussez, S.; Madeddu, G.; Babudieri, S.; Boscolo-Rizzo, P.; et al. New onset of smell and taste loss are common findings also in patients with symptomatic COVID-19 after complete vaccination. Laryngoscope 2022, 132, 419–421. [Google Scholar] [CrossRef]
  39. Lechien, J.R.; Chiesa-Estomba, C.M.; Radulesco, T.; Michel, J.; Vaira, L.A.; Le Bon, S.D.; Horoi, M.; Falanga, C.; Barillari, M.R.; Hans, S.; et al. Clinical features of patients who had two COVID-19 episodes: A European multicentre case series. J. Intern. Med. 2021, 290, 421–429. [Google Scholar] [CrossRef]
  40. Armando, F.; Beythien, G.; Kaiser, F.K.; Allnoch, L.; Heydemann, L.; Rosiak, M.; Becker, S.; Gonzalez-Hernandez, M.; Lamers, M.M.; Haagmans, B.L.; et al. SARS-CoV-2 Omicron variant causes mild pathology in the upper and lower respiratory tract of hamsters. Nat. Commun. 2022, 13, 3519. [Google Scholar] [CrossRef]
  41. Bauer, L.; Rissmann, M.; Benavides, F.F.W.; Leikten, L.; van Run, P.; Begeman, L.; Velghuis, E.J.B.; Lendemeijer, B.; Smeenk, H.; de Vrij, F.M.S.; et al. In vitro and in vivo differences in neurovirulence between D614G, delta and omicron BA.1 SARS-Cov-2 variants. Acta Neuropathol. Commun. 2022, 10, 124. [Google Scholar] [CrossRef] [PubMed]
  42. Meng, B.; Abdullahi, A.; Ferreira, I.A.T.M.; Goonawardane, N.; Saito, A.; Kimura, I.; Yamasoba, D.; Pereyra Gerber, P.; Fatihi, S.; Rathore, S.; et al. Altered TMPRSS2 usage by SARS-CoV-2 omicron impacts infectivity and fusogenicity. Nature 2022, 603, 706–714. [Google Scholar] [CrossRef] [PubMed]
  43. Lechien, J.R.; Radulesco, T.; Calvo-Henriquez, C.; Chiesa-Estomba, C.M.; Hans, S.; Barillari, M.R.; Cammaroto, G.; Descamps, G.; Hsieh, J.; Vaira, L.; et al. ACE2 & TMPRSS2 expressions in head & neck tissues: A systemic review. Head Neck Pathol. 2021, 15, 225–235. [Google Scholar] [PubMed]
  44. Butowt, R.; Bilinska, K.; von Barheld, C. Why does the Omicron variant largely spare olfactory function? Implications for the pathogenesis of anosmia in coronavirus disease 2019. J. Infect. Dis. 2022, 226, 1204–1208. [Google Scholar] [CrossRef]
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MDPI and ACS Style

Vaira, L.A.; Lechien, J.R.; De Riu, G.; Saussez, S. The Trajectories of Olfactory Dysfunction from the First to the Omicron Wave: Are We Getting over it? Pathogens 2023, 12, 10. https://doi.org/10.3390/pathogens12010010

AMA Style

Vaira LA, Lechien JR, De Riu G, Saussez S. The Trajectories of Olfactory Dysfunction from the First to the Omicron Wave: Are We Getting over it? Pathogens. 2023; 12(1):10. https://doi.org/10.3390/pathogens12010010

Chicago/Turabian Style

Vaira, Luigi Angelo, Jérome R. Lechien, Giacomo De Riu, and Sven Saussez. 2023. "The Trajectories of Olfactory Dysfunction from the First to the Omicron Wave: Are We Getting over it?" Pathogens 12, no. 1: 10. https://doi.org/10.3390/pathogens12010010

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