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Intranasal insulin for COVID-19-related smell loss

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Background

Quantitative (hyposmia and anosmia) and qualitative (phantosmia and parosmia) olfactory disorders are common consequences of COVID-19 infection found in more than 38% of patients even months after resolution of acute disease. SARS-CoV-2 has tropism for angiotensin-converting enzyme 2 (ACE2) in the respiratory system, suggesting that it is the mechanism of damage to the olfactory neuroepithelium and of involvement at the central nervous system. The olfactory bulb is the organ with the highest insulin uptake in the central nervous system. Insulin increases the production of Growth Factors (GF); therefore, in this study, the administration of intranasal insulin is proposed as a viable treatment for olfactory disturbances. The aim of this study was to obtain improvement in olfaction after 4 weeks of intranasal insulin administration in a group of patients presenting chronic olfactory disturbances secondary to COVID-19 infection, quantified using the Threshold, Discrimination, and Identification (TDI) score based on the Sniffin Sticks®.

Methods

Experimental, longitudinal, prolective and prospective study of patients with a previous diagnosis of COVID-19 in the last 3–18 months and who persisted with anosmia or hyposmia. The sample size was calculated with “satulator”. The intervention was performed from January to May 2022. Throughout four appointments, a baseline olfactory measurement was obtained using the TDI score based on the Sniffin Sticks® test. In the first three appointments, Gelfoam® cottonoids soaked in 40 IU of NPH insulin were placed on the nasal roof of each nostril for 15 min. Descriptive statistics, student's paired t test and a multiple linear regression were utilized to ascertain statistical significance of the outcome on the TDI score obtained on the fourth and final appointment.

Results

27 patients were included in the study. Table 1 summarizes the sample characteristics. The results exhibit that 93% of the sample had an improvement. The initial mean TDI score was 67% (63–71) compared to the final mean of 83% (80–86, p < 0.01). TDI subsection analysis is shown in Table 2. There was no significant difference in pre-intervention and post-intervention glucose measurements after the intranasal insulin administration.

Conclusions

The administration of intranasal insulin has promising results, pointing towards an alternative of treatment for chronic olfactory disturbances secondary to neuroepithelial damage caused by upper respiratory tract infections. Furthermore, this is the first study to use a three-point assessment of olfaction in post-COVID-19 patients, while using the Sniffin Sticks® TDI score adapted to Latin Spanish.

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Data availability

The data that support the findings of this study are available from the corresponding author, [Dibildox D.], upon reasonable request.

References

  1. Croy I, Nordin S, Hummel T (2014) Olfactory disorders and quality of life–an updated review. Chem Senses 39(3):185–194. https://doi.org/10.1093/chemse/bjt072. (Epub 2014 Jan 15)

    Article  PubMed  Google Scholar 

  2. Oleszkiewicz A, Schriever VA, Croy I, Hähner A, Hummel T (2019) Updated Sniffin’ Sticks normative data based on an extended sample of 9139 subjects. Eur Arch Oto-Rhino-Laryngol 276(3):719–728. https://doi.org/10.1007/s00405-018-5248-1

    Article  CAS  Google Scholar 

  3. Meng X, Deng Y, Dai Z, Meng Z (2020) COVID-19 and anosmia: a review based on up-to-date knowledge. Am J Otolaryngol 41(5):102581. https://doi.org/10.1016/j.amjoto.2020.102581. (Epub 2020 Jun 2)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL (2020) Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol 10(8):944–950. https://doi.org/10.1002/alr.22587. (Epub 2020 Jun 18)

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hopkins C, Surda P, Whitehead E, Kumar BN (2020) Early recovery following new onset anosmia during the COVID-19 pandemic—an observational cohort study. J Otolaryngol Head Neck Surg 49(1):26. https://doi.org/10.1186/s40463-020-00423-8

    Article  PubMed  PubMed Central  Google Scholar 

  6. Vaira LA, Salzano G, Fois AG, Piombino P, De Riu G (2020) Potential pathogenesis of ageusia and anosmia in COVID-19 patients. Int Forum Allergy Rhinol 10(9):1103–1104. https://doi.org/10.1002/alr.22593. (Epub 2020 Jun 15)

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mutiawati E, Fahriani M, Mamada SS, Fajar JK, Frediansyah A, Maliga HA et al (2021) Anosmia and dysgeusia in SARS-COV-2 infection: Incidence and effects on covid-19 severity and mortality, and the possible pathobiology mechanisms—a systematic review and meta-analysis. F1000Research 10:40. https://doi.org/10.12688/f1000research.28393.1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC 3rd (2020) COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg 163(1):132–134. https://doi.org/10.1177/0194599820922992. (Epub 2020 Apr 28)

    Article  PubMed  Google Scholar 

  9. Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V et al (2020) Features of anosmia in COVID-19. Med Mal Infect 50(5):436–439. https://doi.org/10.1016/j.medmal.2020.04.006. (Epub 2020 Apr 17)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Kosugi EM, Lavinsky J, Romano FR, Fornazieri MA, Luz-Matsumoto GR, Lessa MM, Piltcher OB, Sant’Anna GD (2020) Incomplete and late recovery of sudden olfactory dysfunction in COVID-19. Braz J Otorhinolaryngol 86(4):490–496. https://doi.org/10.1016/j.bjorl.2020.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  11. Xu L, Liu J, Wroblewski KE, McClintock MK, Pinto JM (2020) Odor sensitivity versus Odor identification in older US adults: associations with cognition, age, gender, and race. Chem Senses 45(4):321–330. https://doi.org/10.1093/chemse/bjaa018

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dibildox D, Loyola-Nieto P, Brenner-Muslera E, Guerra-Arellano D, Loyola-Nieto F, Maldonado-Cobá A (2022) Implementación y adaptación de la prueba olfatoria Sniffin sticks en población mexicana con trastornos olfatorios pos-COVID-19 usando el índice TDI. An Orl Mex 67(3):201–206

    Google Scholar 

  13. Abdelalim AA, Mohamady AA, Elsayed RA, Elawady MA, Ghallab AF (2021) Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: a randomized controlled trial. Am J Otolaryngol 42(2):102884. https://doi.org/10.1016/j.amjoto.2020.102884. (Epub 2021 Jan 4)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Rashid RA, Alaqeedy AA, Al-Ani RM (2022) Parosmia due to COVID-19 disease: a 268 case series. Indian J Otolaryngol Head Neck Surg 74(2):2970–2977. https://doi.org/10.1007/s12070-021-02630-9. (Epub 2021 May 23)

    Article  PubMed  Google Scholar 

  15. Zhang Y, Mei T, Chen Y, Wang L, Jiang L, Liu K, Zhao L, Luo Z, Chi W, Zhu X (2021) Smell disorders in COVID-19 patients: role of olfactory training: a protocol for systematic review and meta-analysis. Medicine (Baltimore) 100(8):e24862. https://doi.org/10.1097/MD.0000000000024862

    Article  PubMed  CAS  Google Scholar 

  16. Koyama S, Kondo K, Ueha R, Kashiwadani H, Heinbockel T (2021) Possible use of phytochemicals for recovery from COVID-19-induced Anosmia and Ageusia. Int J Mol Sci 22(16):8912. https://doi.org/10.3390/ijms22168912

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Rezaeian A (2018) Effect of intranasal insulin on olfactory recovery in patients with hyposmia: a randomized clinical trial. Otolaryngol Head Neck Surg 158(6):1134–1139. https://doi.org/10.1177/0194599818764624. (Epub 2018 Mar 20)

    Article  PubMed  Google Scholar 

  18. Mohamad SA, Badawi AM, Mansour HF (2021) Insulin fast-dissolving film for intranasal delivery via olfactory region, a promising approach for the treatment of anosmia in COVID-19 patients: design, in-vitro characterization and clinical evaluation. Int J Pharm 601:120600. https://doi.org/10.1016/j.ijpharm.2021.120600. (Epub 2021 Apr 14)

    Article  PubMed  CAS  Google Scholar 

  19. Butowt R, von Bartheld CS (2021) Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist 27(6):582–603. https://doi.org/10.1177/1073858420956905. (Epub 2020 Sep 11)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

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Funding

Funding sources for the study were covered by the author Daniel Dibildox.

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Authors and Affiliations

  1. Hospital Medica Sur, Mexico City, Mexico

    Dibildox Daniel

  2. Faculty of Health Sciences, Panamerican University, Mexico City, Mexico

    Loyola-Nieto Paula, Brenner-Muslera Eduardo, Guerra-Arellano Daniel, Dib-Estephan Andrea, Loyola-Nieto Fernando & Maldonado-Cobá Armando

Authors
  1. Dibildox Daniel
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  2. Loyola-Nieto Paula
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  3. Brenner-Muslera Eduardo
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  4. Guerra-Arellano Daniel
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  5. Dib-Estephan Andrea
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  6. Loyola-Nieto Fernando
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  7. Maldonado-Cobá Armando
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Contributions

All authors wrote the protocol and collected the patient data, Brenner–Muslera analysed and interpreted the patient data. All Authors read and approved the final manuscript.

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Correspondence to Dibildox Daniel.

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The authors declare that they have no conflict of interests.

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This study followed the Declaration of Helsinki. Its design was approved by the ethics committee of the Faculty of Health Sciences of the Panamerican University.

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Daniel, D., Paula, LN., Eduardo, BM. et al. Intranasal insulin for COVID-19-related smell loss. Eur Arch Otorhinolaryngol 281, 201–205 (2024). https://doi.org/10.1007/s00405-023-08176-6

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  • DOI: https://doi.org/10.1007/s00405-023-08176-6

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