Morphological features of changes in peripheral olfactory structures in SARS-COV-2 coronavirus infection
DOI:
https://doi.org/10.14739/2310-1237.2021.3.234369Keywords:
COVID-19, SARS-CoV-2, coronavirus infections, olfaction disorders, olfactory epithelium, olfactory bulb, olfactory tractAbstract
Coronavirus infection caused by the SARS-CoV-2 virus is an extremely important and urgent problem of modern medicine. It spreads quickly, has a high probability of a severe course and a large number of critical complications in patients from the risk group. The presence of pathognomonic symptoms, one of which is the development of hypo– or anosmia, makes it possible to quickly differentiate coronavirus infection from other acute respiratory viral infections, that is, to isolate the patient on time and begin correct treatment, taking all possible risks into account.
The aim is to identify the morphological features of olfactory structural elements in patients with coronavirus disease (COVID-19) for a better understanding of the mechanisms of olfactory disorders development in coronavirus infection.
Materials and methods. The basis of the work is a retrospective analysis of autopsy material, namely the mucous membrane of the upper parts of the nasal cavity (olfactory epithelium) and olfactory bulbs of nine deceased (4 women and 5 men) aged from 53 to 79 years with a laboratory-confirmed diagnosis of COVID-19 and anosmia in anamnesis. We used standard hematoxylin and eosin staining and immunohistochemical reactions in accordance with the TermoScientific protocols (USA) with antibodies to neurospecific beta-III tubulin (clone TuJ-1) and RnDsystems protocols with antibodies to olfactory marker protein (OMP) and angiotensin converting enzyme (ACE-2). To compare the results, a control group of 9 deaths (3 women and 6 men) aged from 59 to 68 years with a laboratory-refuted diagnosis of COVID-19 was formed. The causes of death of these patients were complications of diabetes, coronary heart disease and cerebrovascular disorders of the ischemic
type.
Results. The average age of the deceased with a laboratory-confirmed diagnosis of COVID-19 and a history of anosmia and the control group was 64.67 ± 7.73 and 62.33 ± 6.48 years, respectively. The expression of olfactory marker protein (OMP) and neurospecific beta-III tubulin (clone TuJ-1) was partially positive (40.89 (25.00–52.00) and 42.44 (29.00–55.00) cells in the field of view at a magnification of 200×, respectively) in seven out of nine sections of the olfactory mucous membrane of deaths with a laboratory-confirmed diagnosis of COVID-19 and anosmia in anamnesis. The reaction with antibodies to angiotensin converting enzyme (ACE-2) was focally or subtotally absent (34.33 (14.00–49.00) cells in the field of view at 200× magnification). There was expression of these three markers in control sections of the olfactory mucosa of a deceased with a laboratory excluded diagnosis of COVID-19 and no symptoms of anosmia (Mann–Whitney test, P < 0.05). In sections of olfactory bulbs of patients with COVID-19 weak (Mann–Whitney test, P < 0.05) expression of receptors for angiotensin-converting enzyme (ACE-2) (26.78 (15.00–39.00) cells in field of view at a magnification of 200×) was revealed in contrast to control sections (100.56 (94.00–107.00) cells in the field of view at a magnification of 200×).
Conclusions. The development of anosmia in SARS-CoV-2 coronavirus infection has specific features. This may be due to the primary destruction of cells expressing receptors for the angiotensin-converting enzyme (ACE-2-positive: sustentacular cells of the olfactory mucosa, neurons of the olfactory bulbs). Subsequent dysfunction of olfactory cells (OMP- and TuJ-1-positive) is also possible.
References
Bilinska, K., Jakubowska, P., Von Bartheld, C. S., & Butowt, R. (2020). Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age. ACS chemical neuroscience, 11(11), 1555-1562. https://doi.org/10.1021/acschemneuro.0c00210
Butowt, R., & von Bartheld, C. S. (2020). Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. The Neuroscientist, 1073858420956905. Advance online publication. https://doi.org/10.1177/1073858420956905
Meinhardt, J., Radke, J., Dittmayer, C., Franz, J., Thomas, C., Mothes, R., Laue, M., Schneider, J., Brünink, S., Greuel, S., Lehmann, M., Hassan, O., Aschman, T., Schumann, E., Chua, R. L., Conrad, C., Eils, R., Stenzel, W., Windgassen, M., Rößler, L., … Heppner, F. L. (2021). Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nature neuroscience, 24(2), 168-175. https://doi.org/10.1038/s41593-020-00758-5
Chen, C. R., Kachramanoglou, C., Li, D., Andrews, P., & Choi, D. (2014). Anatomy and cellular constituents of the human olfactory mucosa: a review. Journal of neurological surgery. Part B, Skull base, 75(5), 293-300. https://doi.org/10.1055/s-0033-1361837
Saussez, S., Lechien, J. R., & Hopkins, C. (2021). Anosmia: an evolution of our understanding of its importance in COVID-19 and what questions remain to be answered. European archives of oto-rhino-laryngology, 278(7), 2187-2191. https://doi.org/10.1007/s00405-020-06285-0
Tong, J. Y., Wong, A., Zhu, D., Fastenberg, J. H., & Tham, T. (2020). The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis. Otolaryngology--head and neck surgery, 163(1), 3-11. https://doi.org/10.1177/0194599820926473
Vaira, L. A., Salzano, G., Fois, A. G., Piombino, P., & De Riu, G. (2020). Potential pathogenesis of ageusia and anosmia in COVID-19 patients. International forum of allergy & rhinology, 10(9), 1103-1104. https://doi.org/10.1002/alr.22593
van Riel, D., Verdijk, R., & Kuiken, T. (2015). The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system. The Journal of pathology, 235(2), 277-287. https://doi.org/10.1002/path.4461
Vedin, V., Slotnick, B., & Berghard, A. (2004). Zonal ablation of the olfactory sensory neuroepithelium of the mouse: effects on odorant detection. The European journal of neuroscience, 20(7), 1858-1864. https://doi.org/10.1111/j.1460-9568.2004.03634.x
Williams, F., Freidin, M. B., Mangino, M., Couvreur, S., Visconti, A., Bowyer, R., Le Roy, C. I., Falchi, M., Mompeó, O., Sudre, C., Davies, R., Hammond, C., Menni, C., Steves, C. J., & Spector, T. D. (2020). Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable. Twin research and human genetics, 23(6), 316-321. https://doi.org/10.1017/thg.2020.85
Xu, H., Zhong, L., Deng, J., Peng, J., Dan, H., Zeng, X., Li, T., & Chen, Q. (2020). High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. International journal of oral science, 12(1), 8. https://doi.org/10.1038/s41368-020-0074-x
Xydakis, M. S., Dehgani-Mobaraki, P., Holbrook, E. H., Geisthoff, U. W., Bauer, C., Hautefort, C., Herman, P., Manley, G. T., Lyon, D. M., & Hopkins, C. (2020). Smell and taste dysfunction in patients with COVID-19. The Lancet. Infectious diseases, 20(9), 1015-1016. https://doi.org/10.1016/S1473-3099(20)30293-0
Yan, C. H., Faraji, F., Prajapati, D. P., Ostrander, B. T., & DeConde, A. S. (2020). Self-reported olfactory loss associates with outpatient clinical course in COVID-19. International forum of allergy & rhinology. 10(7), 821-831. https://doi.org/10.1002/alr.22592
Ziegler, C., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., Cao, Y., Yousif, A. S., Bals, J., Hauser, B. M., Feldman, J., Muus, C., Wadsworth, M. H., 2nd, Kazer, S. W., Hughes, T. K., Doran, B., Gatter, G. J., Vukovic, M., Taliaferro, F., Mead, B. E., … HCA Lung Biological Network (2020). 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, 181(5), 1016-1035.e19. https://doi.org/10.1016/j.cell.2020.04.035
Zubair, A. S., McAlpine, L. S., Gardin, T., Farhadian, S., Kuruvilla, D. E., & Spudich, S. (2020). Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA neurology, 77(8), 1018-1027. https://doi.org/10.1001/jamaneurol.2020.2065
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