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Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection
Open accessAbstract
In recent months it has emerged that the novel coronavirus—responsible for the COVID-19 pandemic—causes reduction of smell and taste in a large fraction of patients. The chemosensory deficits are often the earliest, and sometimes the only signs in otherwise asymptomatic carriers of the SARS-CoV-2 virus. The reasons for the surprisingly early and specific chemosensory dysfunction in COVID-19 are now beginning to be elucidated. In this hypothesis review, we discuss implications of the recent finding that the prevalence of smell and taste dysfunction in COVID-19 patients differs between populations, possibly because of differences in the spike protein of different virus strains or because of differences in the host proteins that enable virus entry, thus modifying infectivity. We review recent progress in defining underlying cellular and molecular mechanisms of the virus-induced anosmia, with a focus on the emerging crucial role of sustentacular cells in the olfactory epithelium. We critically examine the current evidence whether and how the SARS-CoV-2 virus can follow a route from the olfactory epithelium in the nose to the brain to achieve brain infection, and we discuss the prospects for using the smell and taste dysfunctions seen in COVID-19 as an early and rapid diagnostic screening tool.
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“Such chemosensory deficits experienced in COVID‐19 are often short‐lived, with most symptoms resolving in 7‐10 days, with sense of smell often returning slightly earlier than taste.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [299]
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Cites
Clinical characteristics of coronavirus disease 2019 in China
Guan, W.-J., Ni, Z.-Y., Hu, Y., Liang, W.-H., Ou, C.-Q., He, J.-X., Liu, L., Shan, H., Lei, C.-L., Hui, D. S. C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002032 · Cited by 30,246
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30211-7 · Cited by 21,415
A new coronavirus associated with human respiratory disease in China
Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., Hu, Y., Tao, Z.-W., Tian, J.-H., Pei, Y.-Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2008-3 · Cited by 11,688
Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China
Mao, L., Jin, H., Wang, M., Hu, Y., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1127 · Cited by 7,166
Detection of SARS-CoV-2 in Different Types of Clinical Specimens
Wang, W., Xu, Y., Gao, R., Lu, R., Han, K., Wu, G., & Tan, W. (2020) · JAMA · doi:10.1001/jama.2020.3786 · Cited by 5,116
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients
Zou, L., Ruan, F., Huang, M.-X., Liang, L.-J., Huang, H., Hong, Z.-S., Yu, J.-X., Kang, M., Song, Y.-C., Xia, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2001737 · Cited by 4,590
Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.043 · Cited by 4,281
Structural basis of receptor recognition by SARS-CoV-2
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020) · Nature · doi:10.1038/s41586-020-2179-y · Cited by 3,661
High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa
Xu, H., Zhong, L., Deng, J., Peng, J., Dan, H., Zeng, X., Li, T., & Chen, Q. (2020) · International Journal of Oral Science · doi:10.1038/s41368-020-0074-x · Cited by 2,838
Lechien, J. R., Chiesa-Estomba, C. M., De Siati, D. R., Horoi, M., Le Bon, S. D., Rodriguez, A., Dequanter, D., Blecic, S., El Afia, F., Distinguin, L., et al. (2020) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-020-05965-1 · Cited by 2,668
Research works printed but not linked: 17
- Asselta R, 2020, Aging (Albany NY), 12, 98
- 10.1101/2020.04.03.20047977 · DOI
- 10.1101/2020.06.16.151704 · DOI
- 10.1101/2020.05.08.084996 · DOI
- Dos Santos NPC, 2020, MedRxiv Preprint
- 10.1101/2020.07.04.20145870 · DOI
- Hwang CS, 2006, Acta Neurol Taiwan, 15
- 10.1016/0002-378 · DOI
- 10.1101/2020.07.15.204602 · DOI
- 10.1101/2020.06.08.139329 · DOI
- Netland J, 2008, J Virol, 82
- 10.1101/2020.05.04.20090902 · DOI
- Passarelli PC, 2020, Am J Dent, 33
- 10.1101/2020.05.14.097204 · DOI
- 10.1101/2020.06.15.20132134 · DOI
- 10.1101/2020.06.17.20106302 · DOI
- Yang XH, 2007, Comp Med, 57
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Flerlage, T., Boyd, D. F., Meliopoulos, V., Thomas, P. G., & Schultz‐Cherry, S. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00542-7 · Cited by 419
von Bartheld, C. S., Hagen, M. M., & Butowt, R. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00460 · Cited by 294
Self-citationZazhytska, M., Kodra, A. L., Hoagland, D. A., Frere, J. J., Fullard, J. F., Shayya, H. J., McArthur, N. G., Møller, R., Uhl, S. A., Omer, A. D., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.024 · Cited by 260
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BackgroundInfluentialTan, 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. (2022) · BMJ · doi:10.1136/bmj-2021-069503 · Cited by 241
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Self-citationAddison, A. B., Wong, B. L. K., Ahmed, T., Macchi, A., Konstantinidis, I., Huart, C., Frasnelli, J., Fjældstad, A. W., Ramakrishnan, V. R., Rombaux, P., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.12.641 · Cited by 148
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BackgroundNeurological complications and infection mechanism of SARS-CoV-2
Wan, D., Du, T., Hong, W., Chen, L., Que, H., Lu, S., & Peng, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00818-7 · Cited by 140
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Beckman, D., Bonillas, A. C., Diniz, G. B., Ott, S. P., Roh, J. W., Elizaldi, S. R., Schmidt, B., Sammak, R. L., Rompay, K. K. A. V., Iyer, S. S., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111573 · Cited by 132
International consensus statement on allergy and rhinology: Olfaction
Patel, Z. M., Holbrook, E. H., Turner, J. H., Adappa, N. D., Albers, M. W., Altundağ, A., Appenzeller, S., Costanzo, R. M., Croy, I., Davis, G. E., et al. (2022) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22929 · Cited by 142
Mutiawati, E., Fahriani, M., Mamada, S. S., Fajar, J. K., Frediansyah, A., Maliga, H. A., Ilmawan, M., Emran, T. B., Ophinni, Y., Ichsan, I., et al. (2021) · F1000Research · doi:10.12688/f1000research.28393.1 · Cited by 127
Boscolo‐Rizzo, P., Hummel, T. R., Hopkins, C. L., Dibattista, M., Menini, A., Spinato, G., Fabbris, C., Emanuelli, E., D’Alessandro, A., Marzolino, R., et al. (2021) · Rhinology Journal · doi:10.4193/rhin21.249 · Cited by 128
“While the expression of ACE2 receptor in sustentacular cells of the olfactory neuroepithelium (OE) was consistently demonstrated in several studies ((35)), the expression of the ACE2 receptor in taste buds was confirmed only in a very recent investigation demonstrating the colocalization of ACE2 receptor, SARS-CoV-2,…”
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Shelton, J. F., Shastri, A. J., Fletez‐Brant, K., The 23andMe COVID-19 Team, Auton, A., Chubb, A., Fitch, A., Kung, A., Altman, A., Kill, A., et al. (2022) · Nature Genetics · doi:10.1038/s41588-021-00986-w · Cited by 129
Butowt, R., Meunier, N., Bryche, B., & von Bartheld, C. S. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02314-2 · Cited by 127
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Butowt, R., Bilińska, K., & von Bartheld, C. S. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.11.003 · Cited by 136
“provides a plausible mechanism for COVID-19 induced anosmia [10-11,24,62].”
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Magusali, N., Graham, A. C., Piers, T. M., Panichnantakul, P., Yaman, U., Shoai, M., Reynolds, R. H., Botia, J. A., Brookes, K. J., Guetta-Baranes, T., et al. (2021) · Brain · doi:10.1093/brain/awab337 · Cited by 111
“41–45 There is accumulating evidence that these brain structures and cells are infected with SARS-CoV-2 and are altering the cytokine profile of the brain.”
BackgroundBoscolo‐Rizzo, P., Tirelli, G., Meloni, P., Hopkins, C. L., Madeddu, G., VITO, A. D., Gardenal, N., Valentinotti, R., Tofanelli, M., Borsetto, D., et al. (2022) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22995 · Cited by 106
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Manzini, I., Schild, D., & Natale, C. D. (2021) · Physiological Reviews · doi:10.1152/physrev.00036.2020 · Cited by 90
Wang, W. B., Liang, Y., Jin, Y. Q., Zhang, J., Su, J. G., & Li, Q. M. (2021) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2021.108035 · Cited by 83
“Compared with the original SARS-CoV-2 strains, the 501Y.V1, 501Y.V2 and 501Y.V3 variants are potentially more transmissible, which may also reduce the effectiveness of the current vaccines and neutralizing antibodies[27].”
InfluentialAssociation of COVID-19 with Comorbidities: An Update
Chatterjee, S., Nalla, L. V., Sharma, M., Sharma, N., Singh, A. A., Malim, F. M., Ghatage, M., Mukarram, M., Pawar, A., Parihar, N., et al. (2023) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.2c00181 · Cited by 91
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BackgroundSarubbo, F., Haji, K. E., Vidal-Balle, A., & Bargay, J. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100399 · Cited by 71
“Bibliography published so far include cohort studies and case reports, being the prevalence of anosmia in COVID-19 patients calculated to be around 44%, and the prevalence of hypogeusia around 43% (Butowt and von Bartheld, 2020).”
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“H ) The SARS-CoV-2 via the ACE2 receptor on the centers (olfactory bulb and cortex), thereby reducing smell sensations [150–156].”
Backgroundvon Bartheld, C. S., Hagen, M. M., & Butowt, R. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00542 · Cited by 61
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Song, J., Deng, Y., Wang, H., Wang, Z., Liao, B., Ma, J., He, C., Li, P., Liu, Y., Alobid, I., et al. (2021) · Current Medical Science · doi:10.1007/s11596-021-2312-7 · Cited by 58
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Neta, F. I., Fernandes, A. C. L., Vale, A. J. M., Pinheiro, F. I., Cobucci, R. N., de Azevedo, E. P., & Gúzen, F. P. (2021) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2021.100035 · Cited by 55
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Vance, H., Maslach, A., Stoneman, E. K., Harmes, K. M., Ransom, A., Seagly, K., & Furst, W. (2021) · The Journal of the American Board of Family Medicine · doi:10.3122/jabfm.2021.06.210254 · Cited by 49
“32 Although the explanation is currently not clear, 33 possible explanations as to what may cause anosmia during COVID-19 infection include congestion, damage to the olfactory nerve, in fl ammation in cells within the lining of the nasal cavity, and viral effects on the cranial nerves within the…”
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BackgroundReyna, R. A., Kishimoto‐Urata, M., Urata, S., Makishima, T., Paessler, S., & Maruyama, J. (2022) · Scientific Reports · doi:10.1038/s41598-021-04622-9 · Cited by 53
Mohamad, S. A., Badawi, A. M., & Mansour, H. F. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120600 · Cited by 47
Bussière, N., Mei, J., Lévesque-Boissonneault, C., Blais, M., Carazo, S., Gros‐Louis, F., Serres, G. D., Dupré, N., & Frasnelli, J. (2021) · Chemical Senses · doi:10.1093/chemse/bjab038 · Cited by 46
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Shrewsbury, S. B. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15061720 · Cited by 48
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Veronese, N., Bonica, R., Cotugno, S., Tulone, O., Camporeale, M., Smith, L., Trott, M., Bruyère, O., Mirarchi, L., Rizzo, G., et al. (2022) · Viruses · doi:10.3390/v14091863 · Cited by 40
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Jaffal, S. M., & Abbas, M. A. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109567 · Cited by 37
“TRP channels anosmia, ageusia and hearing loss in COVID-19 Worldwide, it was emerged that COVID-19 infection causes a reduction or loss of taste and smell [77].”
Chaaban, N., Høier, A. T. Z. B., & Andersen, B. V. (2021) · Foods · doi:10.3390/foods10040892 · Cited by 44
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Krishnakumar, H. N., Momtaz, D., Sherwani, A., Mhapankar, A., Gonuguntla, R. K., Maleki, A., Abbas, A., Ghali, A. N., & Afif, A. A. (2022) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-022-07689-w · Cited by 38
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Wu, H., Sun, Q., Yuan, S., Wang, J., Li, F., Gao, H., Chen, X., Yang, R., & Xu, J. (2022) · Cardiovascular Toxicology · doi:10.1007/s12012-022-09730-0 · Cited by 37
Revealing the mystery of persistent smell loss in long COVID patients
Park, J. W., Wang, X., & Xu, R. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.73485 · Cited by 38
“First, East Asian populations displayed a 2-3-fold lower rate of olfactory and taste defects than the populations in western countries [53].”
BackgroundInterventions for the treatment of persistent post-COVID-19 olfactory dysfunction
O’Byrne, L. M., Webster, K. E., MacKeith, S. A. C., Philpott, C. M., Hopkins, C. L., & Burton, M. J. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013876.pub3 · Cited by 37
The Pathogenesis of Cytomegalovirus and Other Viruses Associated with Hearing Loss: Recent Updates
Shi, X., Liu, X., & Sun, Y. (2023) · Viruses · doi:10.3390/v15061385 · Cited by 39
A Systematic Review of Imaging Studies in Olfactory Dysfunction Secondary to COVID-19
Keshavarz, P., Haseli, S., Yazdanpanah, F., Bagheri, F., Raygani, N., & Karimi‐Galougahi, M. (2021) · Academic Radiology · doi:10.1016/j.acra.2021.08.010 · Cited by 35
COVID-19 and Alzheimer’s Disease: A Literature Review
Hardan, L., Filtchev, D., Kassem, R., Bourgi, R., Łukomska−Szymańska, M., Tarhini, H., Salloum-Yared, F., Mancino, D., Kharouf, N., & Haïkel, Y. (2021) · Medicina · doi:10.3390/medicina57111159 · Cited by 39
“MRI hypersignals of the olfactory epithelial cortex indicate infection especially with the presence of ACE2 receptors and TMPRSS2 in the olfactory epithelium [36].”
BackgroundSzabo, M. P., Iba, M., Nath, A., Masliah, E., & Kim, C. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00755-7 · Cited by 37
SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t
Lingor, P., Demleitner, A. F., Wolff, A. W., & Feneberg, E. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-022-02500-w · Cited by 37
“In a more detailed study of the olfactory mucosa, the virus was found in sustentacular and stem cells of the mucosa while absent from olfactory receptor neurons (ORN) (Butowt and von Bartheld 2020).”
BackgroundRethinavel, H. S., Ravichandran, S., Radhakrishnan, R. K., & Kandasamy, M. (2021) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2021.101965 · Cited by 36
New Brazilian variant of the SARS-CoV-2 (P1/Gamma) of COVID-19 in Alagoas state
da Silva, J. C., Félix, V., Leão, S. A. B. F., Filho, E. M. T., & Scorza, F. A. (2021) · The Brazilian Journal of Infectious Diseases · doi:10.1016/j.bjid.2021.101588 · Cited by 34
“Studies suggest that expression of ACE2 cellular proteins and TMPRSS2 protease in the olfactory epithelium cells are involved in viral access to the human body and detection in oropharyngeal secretions.(2,12) Since ACE2 proteins seem to be expressed in significantly higher levels in older people, this may explain the…”
Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction
Webster, K. E., O’Byrne, L. M., MacKeith, S. A. C., Philpott, C. M., Hopkins, C. L., & Burton, M. J. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013877.pub2 · Cited by 36
Bilińska, K., von Bartheld, C. S., & Butowt, R. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.674123 · Cited by 35
Self-citationVelichkovsky, B. B., Razvaliaeva, A. Y., Khlebnikova, A. A., Manukyan, P. A., & Kasatkin, V. N. (2023) · Acta Psychologica · doi:10.1016/j.actpsy.2023.103838 · Cited by 40
Post-COVID Symptoms in Occupational Cohorts: Effects on Health and Work Ability
Magnavita, N., Arnesano, G., Prinzio, R. R. D., Gasbarri, M., Meraglia, I., Merella, M., & Vacca, M. E. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20095638 · Cited by 33
“Chemosensory deficits are often the earliest, and sometimes the only signs of the SARSCoV-2 virus in otherwise asymptomatic carriers [45].”
BackgroundNobile, B., Durand, M., Olié, É., Guillaume, S., Molès, J., Haffen, É., & Courtet, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.615695 · Cited by 31
Sen, A. (2021) · Medical Hypotheses · doi:10.1016/j.mehy.2021.110627 · Cited by 30
“Surprisingly, the recovery after anosmia is often quicker (especially in mild cases) than the time it takes for neuron replacement, cilia maturation, and the growth of the new axons from the olfactory epithelium to form synapses in the olfactory bulb [26,27].”
Dysautonomia and Implications for Anosmia in Long COVID-19 Disease
Vallée, A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10235514 · Cited by 29
“A possible explanation could be that incomplete X chromosome inhibition may contribute to overexpression of ACE2 [29].”
BackgroundNeuroradiological Basis of COVID ‐19 Olfactory Dysfunction: A Systematic Review and Meta‐Analysis
Tan, C. J., Tan, B. K. J., Tan, X. Y., Liu, H., Teo, C. B., See, A., Xu, S., Toh, S. T., Kheok, S. W., Charn, T. C., et al. (2022) · The Laryngoscope · doi:10.1002/lary.30078 · Cited by 30
“At present, conductive mechanisms of olfactory loss in COVID-19-associated OD have largely been dismissed in favor of sensorineural mechanisms,(60,61) given the absence of significant sinonasal symptoms like nasal obstruction and mucosal congestion in COVID-19 infection.(60,62) However, our findings suggest that condu…”
BackgroundSemyachkina-Glushkovskaya, O. V., Postnov, D. E., Lavrova, A. I., Fedosov, I. V., Borisova, E. G., Nikolenko, V. N., Penzel, T., Kurths, J., & Tuchin, V. V. (2020) · IEEE Journal of Selected Topics in Quantum Electronics · doi:10.1109/jstqe.2020.3045834 · Cited by 30
“One of hypothesis explains that the virus infiltrates the brain, possibly from the nose, and affects olfactory centers (olfactory bulb and cortex), thereby reducing smell sensations [50].”
BackgroundSystematic review and meta-analysis of olfactory and gustatory dysfunction in COVID-19
Liu, N., Yang, D., Zhang, T., Sun, J., Fu, J., & Li, H. (2022) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2022.02.004 · Cited by 28
Vestibular Cochlear Manifestations in COVID-19 Cases
Kaliyappan, K., Chen, Y., & Muthaiah, V. P. K. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.850337 · Cited by 28
de Erausquin, G. A., Snyder, H. M., Brugha, T. S., Seshadri, S. S., Carrillo, M. C., Sagar, R., Huang, Y., Newton, C. R. J. C., Tartaglia, M. C., Teunissen, C. E., et al. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12348 · Cited by 27
Follow-Up of a Cohort of Patients with Post-Acute COVID-19 Syndrome in a Belgian Family Practice
Jamoulle, M., Kazeneza-Mugisha, G., & Zayane, A. (2022) · Viruses · doi:10.3390/v14092000 · Cited by 35
“Cerebral disorders dominate, either by thalamic and subthalamic damage (memory loss), cortical damage (brain fog, anomia, hallucination, paresthesias, abnormal movements), or by bulbar damage (anosmia, dysgeusia, dizziness, orthostatic disorder), although in anosmia, both central and peripheral alterations could be de…”
BackgroundDisruption of nuclear architecture as a cause of COVID-19 induced anosmiaPreprint
Zazhytska, M., Kodra, A. L., Hoagland, D. A., Fullard, J. F., Shayya, H. J., Omer, A. D., Firestein, S., Gong, Q., Canoll, P., Goldman, J. E., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.09.430314 · Cited by 26
Shi, Z., Xi, L., Wang, Y., & Zhao, X. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.3c04875 · Cited by 26
Gunder, N., Dörig, P., Witt, M., Welge–Lüssen, A., Menzel, S., & Hummel, T. R. (2023) · HNO · doi:10.1007/s00106-022-01249-8 · Cited by 25
“This is a possible explanation for the rapid improvement in olfactory function in many cases, since the ORNs themselves are only indirectly affected [12].”
BackgroundHippocampal alterations after SARS-CoV-2 infection: A systematic review
Zorzo, C., Solares, L., Méndez, M., & Méndez-López, M. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114662 · Cited by 26
Stroke in SARS-CoV-2 Infection: A Pictorial Overview of the Pathoetiology
Neshin, S. A. S., Shahjouei, S., Koza, E., Friedenberg, I., Khodadadi, F., Sabra, M., Kobeissy, F. H., Ansari, S., Tsivgoulis, G. K., Li, J., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.649922 · Cited by 25
Callejón-Leblic, M. A., Jiménez, D. I. M., Moreno‐Luna, R., Palacios-García, J. M., Álvarez-Cendrero, M., Vizcarra-Melgar, J., Fernandez-Velez, C., Reyes-Tejero, I. M., Maza-Solano, J. M., García, J. G., et al. (2022) · Life · doi:10.3390/life12081256 · Cited by 24
“Although some groups have made considerable research efforts to elucidate the causes of smell and taste dysfunction in COVID-19 [7,8], the underlying mechanism by which SARS-CoV-2 infection leads to chemosensory dysfunction remains unclear.”
BackgroundParosmia post COVID-19: an unpleasant manifestation of long COVID syndrome
Saniasiaya, J., & Prepageran, N. (2021) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2021-139855 · Cited by 24
Salfi, F., Amicucci, G., Corigliano, D., Viselli, L., D’Atri, A., Tempesta, D., & Ferrara, M. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.06.010 · Cited by 26
Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?
Zeng, M., Wang, D. Y., Mullol, J., & Liu, Z. (2021) · Current Allergy and Asthma Reports · doi:10.1007/s11882-020-00987-5 · Cited by 23
Taste and Smell Impairment in Critically Ill Patients With COVID-19: An Intensive Care Unit Study
Sayın, P., Altınay, M., Çınar, A. S., & Özdemir, H. M. (2020) · Ear Nose & Throat Journal · doi:10.1177/0145561320977464 · Cited by 22
“Because neural structures do not contain ACE2 receptors, non-neural involvement has been suggested as a cause of COVID-19related smell and taste impairment.(8) Most patients with COVID-19 exhibit partial taste and/or smell impairment, which tends to resolve early and spontaneously.”
BackgroundGross and Histopathology of COVID-19 With First Histology Report of Olfactory Bulb Changes
Stoyanov, G. S., Petkova, L., Dzhenkov, D. L., Sapundzhiev, N. R., & Todorov, I. (2020) · Cureus · doi:10.7759/cureus.11912 · Cited by 22
Encephalopathy in COVID-19 Patients
Shah, P., Patel, J., Soror, N., & Kartan, R. (2021) · Cureus · doi:10.7759/cureus.16620 · Cited by 23
“Butowt and von Bartheld reported that neurotropism may be caused by virus-induced inflammation or vascular/systemic routes rather than olfactory neurons given that the sudden loss of smell is followed by a rapid recovery which is less than one week [10].”
BackgroundNeurological Complications of COVID-19: A Review of the Literature
Dale, L. (2022) · Cureus · doi:10.7759/cureus.27633 · Cited by 24
“Pathophysiologically, it is thought that COVID-19’s spike protein interacts with angiotensin-converting enzyme 2 (ACE2), and transaminase protein serine 2 (TMPRSS2) receptors on olfactory neurons [16-17].”
BackgroundShahbaz, M. A., Bernardi, F., Alatalo, A., Sachana, M., Clerbaux, L., Muñoz, A., Parvatam, S., Landesmann, B., Kanninen, K. M., & Coecke, S. (2022) · Cells · doi:10.3390/cells11193027 · Cited by 22
Schirinzi, T., Lattanzi, R., Maftei, D., Grillo, P., Zenuni, H., Boffa, L., Albanese, M., Simonetta, C., Bovenzi, R., Maurizi, R., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.12.017 · Cited by 22
MRI evidence of gray matter loss in COVID ‐19 patients with cognitive and olfactory disorders
Capelli, S., Arrigoni, A., Napolitano, A., Pezzetti, G., Remuzzi, A., Zangari, R., Lorini, F. L., Sessa, M., Caroli, A., & Gerevini, S. (2024) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.52164 · Cited by 24
“Instead, it may be attributed to the virus’s neurotropism: angiotensin-converting enzyme 2 (ACE2) is widely present in the olfactory system and, serving as a viral receptor, it may provide SARS-CoV-2 access to the CNS. 31,32 Propagation of viruses by retrograde axonal transport to the olfactory bulbs and to the CNS ha…”
SARS-CoV-2 invasion of the central nervous: a brief review
Siddiqui, R., Mungroo, M. R., & Khan, N. A. (2021) · Hospital Practice · doi:10.1080/21548331.2021.1887677 · Cited by 21
“the olfactory epithelium, brain infiltration affecting olfactory centers, and loss of olfactory receptor neurons [34].”
BackgroundUeha, R., Ito, T., Furukawa, R., Kitabatake, M., Ouji-Sageshima, N., Ueha, S., Koyama, M., Uranaka, T., Kondo, K., & Yamasoba, T. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.924725 · Cited by 22
Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections
Jacob, S. M., Kapadia, R. K., Soule, T., Luo, H., Schellenberg, K. L., Douville, R. N., & Pfeffer, G. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.914411 · Cited by 24
Modeling the effectiveness of olfactory testing to limit SARS-CoV-2 transmission
Larremore, D. B., Toomre, D. K., & Parker, R. (2021) · Nature Communications · doi:10.1038/s41467-021-23315-5 · Cited by 21
“[20] Rafal Butowt and Christopher S von Bartheld.”
BackgroundInterventions for the prevention of persistent post-COVID-19 olfactory dysfunction
Webster, K. E., O’Byrne, L. M., MacKeith, S. A. C., Philpott, C. M., Hopkins, C. L., & Burton, M. J. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013877.pub3 · Cited by 21
Olfaction and neurocognition after COVID-19: a scoping review
Vilarello, B. J., Jacobson, P. T., Tervo, J. P., Waring, N. A., Gudis, D. A., Goldberg, T. E., Devanand, D. P., & Overdevest, J. B. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1198267 · Cited by 21
“Early investigations have provided preliminary insight into the mechanisms by which COVID-19 acutely affects the olfactory system and whether olfaction provides a window into greater neurological dysfunction caused by the virus (Butowt and Bartheld, 2021; Zazhytska et al., 2022).”
BackgroundDoes the RAAS play a role in loss of taste and smell during COVID-19 infections?
Luchiari, H. R., Giordano, R. J., Sidman, R. L., Pasqualini, R., & Arap, W. (2020) · The Pharmacogenomics Journal · doi:10.1038/s41397-020-00202-8 · Cited by 18
“Possible mechanisms for loss of smell and taste in the course of COVID-19 disease are being explored [2, 3] but no direct role of the Renin-Angiotensinaldosterone system (RAAS) in anosmia and ageusia has been suggested until now.”
Background
Metadata
- Authors
- Butowt, R., & von Bartheld, C. S.
- Affiliations
- Department of Molecular Cell Genetics, L. Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
- Center of Biomedical Research Excellence in Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA
- Venue
- The Neuroscientist
- Publisher
- SAGE Publications
- Published
- 2020-09-11
- Volume
- 27
- Issue
- 6
- Pages
- 582-603
- ISSN
- 1073-8584 (ISSN-L)
- 1089-4098
- PMC
- PMC7488171
- OpenAlex
- W3084613638
- Cited by
- 345
- References
- 143
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 38 · 2023: 73 · 2022: 97 · 2021: 91 · 2020: 8
- FWCI
- 23.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Neuroscientist (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- national institutes of health (GM103554)
- Uniwersytet Mikolaja Kopernika w Toruniu (Excellence Initiative -Research University ID-UB)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- anosmia, COVID-19 pandemic, SARS-CoV-2, olfactory dysfunction, taste disorders, olfactory epithelium, sustentacular cells, asymptomatic carriers
- MeSH terms
- COVID-19, Anosmia, Animals, Brain, Humans, Nasal Mucosa, Smell, Olfactory Perception
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