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Letter Postgrad Med J: first published as 10.1136/postgradmedj-2021-139855 on 31 March 2021. Downloaded from Parosmia post COVID-19: an regenerating capability of the olfactory Acknowledgements We would like to acknowledge neurons, whereby the new regenerated all involved in writing this manuscript. unpleasant manifestation of olfactory neurons sprouts and recon- Contributors JS: Writing, editing, literature review and long COVID syndrome nects to the brain results in a trial-and-­ ­ final approval. PN: Editing, literature review and final error process. As there are approximately approval. 350 types of receptors to detect odours, Funding The authors have not declared a specific human brains interpret smell following a grant for this research from any funding agency in the As we begin to slowly unravel the mystery public, commercial or not-­for-­profit sectors. combination of different signals. It is note- hidden behind the current pandemic, Competing interests None declared. novel clinical manifestations are emerging worthy that olfactory nerve interruption Patient consent for publication Not required. ceaselessly following SARS-CoV­ -2. Olfac- or damage is followed by regeneration tory dysfunction, which has become one of the olfactory receptor bipolar neurons Provenance and peer review Not commissioned; along with central reattachment of their externally peer reviewed. of the sought-­after clinical features of 6 COVID-19, has been associated with less axons. However, part of the axonal This article is made freely available for use in accordance with BMJ’s website terms and conditions severe disease manifestation.1 Yet, the regenerations becomes displaced, leading to this ‘misguided’ regenerating axons to for the duration of the covid-19 pandemic or until previously deemed ‘fortunate’ patients 6 otherwise determined by BMJ. You may use, download with olfactory dysfunction who success- reach abnormal territories of the brain, and print the article for any lawful, non-­commercial fully recovered from COVID-19 are now which leads to parosmia. Parallel to that, purpose (including text and data mining) provided the destruction, as well as regeneration of that all copyright notices and trade marks are being afflicted by another sinister condi- retained. tion known as parosmia, which is found the olfactory receptors, has been reported previously to occur in a patch, checker- © Author(s) (or their employer(s)) 2021. No commercial to be more debilitating than loss of smell. board manner, thus leading to distortion re-­use. See rights and permissions. Published by BMJ. Parosmia or distortion of smell is of smell or parosmia. This information currently regarded as one of the long appears to alter Mozell’s theory of spatio- COVID-19 syndrome or chronic temporal pattern of response to magnitude COVID-19 syndrome. Carfi et al found To cite Saniasiaya J, Narayanan P. Postgrad Med J Epub and latency differences across the mucosa that 87.4% of patients in their study who ahead of print: [please include Day Month Year]. to odorants whereby human nose was doi:10.1136/postgradmedj-2021-139855 recovered from COVID-19 had at least suggested to separate vapour or odorant in one persistent symptom with loss of smell Accepted 25 March 2021 a similar pattern to a gas chromatograph.7 among them.2 However, recent reports Postgrad Med J 2021;0:1. Although parosmia following recovery have discovered that a number of patients doi:10.1136/postgradmedj-2021-139855 from postviral olfactory loss has long with loss of smell or regained been reported,8 in patients recovering ORCID iD their smell, yet surprisingly this time, the Jeyasakthy Saniasiaya http://orcid.​ ​org/0000-​ ​0003-​ from COVID-19 it must be a distressing smell was distorted. The magical aroma 1974-4379​ situation. Having said that, the bright of coffee had turned into a nightmare as side of parosmia is that it denotes gradual coffee began to smell pungent like gaso- REFERENCES recovery of smell function. Parosmia has line and favourite dishes were turning to 1 Saniasiaya J, Islam MA, Abdullah B. Prevalence of been reported to be associated with spon- smell more like rotten food or garbage, olfactory dysfunction in coronavirus disease 2019 taneous olfactory recovery suggesting (COVID-19): a meta-­analysis of 27,492 patients. which inadvertently affects as food 9 Laryngoscope 2021;131:865–78.

positive clinical outcome. Although http://pmj.bmj.com/ becomes almost unpalatable. still in infancy, promising reports on 2 Carfì A, Bernabei R, Landi F, et al. Persistent The word parosmia is taken from the symptoms in patients after acute COVID-19. JAMA the outcome of olfactory retraining Greek words: para and osme (smell) 2020;324:603–5. therapy for patients with parosmia post 3 Stenner M, Vent J, Hüttenbrink K-­B, et al. which is defined as a distortion of smell COVID-19 are rising. Olfactory retraining Topical therapy in anosmia: relevance of steroid-­ with the presence of odorant, whereas therapy aims to strengthen olfactory responsiveness. Laryngoscope 2008;118:1681–6. is a condition when there is 4 Butowt R, von Bartheld CS. Anosmia in COVID-19: recovery according to the neuronal plas- a distortion of smell with the absence of 10 underlying mechanisms and assessment of an ticity of the . In the on September 23, 2021 by guest. Protected copyright. odorant. Anosmia, on the other hand, olfactory route to brain infection. Neuroscientist same vein, olfactory retraining therapy 2020;11:107385842095690. means complete loss of smell. boosts cognitive processing of the incom- 5 Gane SB, Kelly C, Hopkins C. Isolated sudden onset As of the latest report, three hypoth- plete sensory information in patients anosmia in COVID-19 infection. A novel syndrome. eses exist to explain the pathophysiology Rhinology 2020;58:289–94. with parosmia.10 Olfactory retraining of olfactory dysfunction secondary to 6 Graziadei PP, Levine RR, Monti Graziadei GA. therapy basically allows patients to relearn Plasticity of connections of the olfactory sensory COVID-19, which include: (1) Mechan- smell by consciously sniffing at least four neuron: regeneration into the forebrain following ical obstruction ensuing the inflammation different odorants two times per day for bulbectomy in the neonatal mouse. Neuroscience around the olfactory cleft, which prevents 1979;4:713–27. several months. the odorants from binding with the olfac- 7 Hornung DE, Mozell MM. Factors influencing the tory receptors,3 (2) infection of the ACE-2 differential sorption of odorant molecules across the Jeyasakthy Saniasiaya ‍ ‍ , olfactory mucosa. J Gen Physiol 1977;69:343–61. expressing supporting cell, mainly the Prepageran Narayanan 8 Seiden AM, Duncan HJ. The diagnosis of a conductive sustentacular cell of the olfactory epithe- olfactory loss. Laryngoscope 2001;111:9–14. Department of Otorhinolaryngology, Faculty of 4 9 Cavazzana A, Larsson M, Münch M, et al. lium and (3) direct invasion of olfactory Medicine, University of Malaya, Kuala Lumpur, Malaysia neurons by SARS-CoV­ -2, which impedes Postinfectious olfactory loss: a retrospective study on the olfaction transmission.5 Correspondence to Dr Jeyasakthy Saniasiaya, 791 patients. Laryngoscope 2018;128:10–15. Department of Otorhinolaryngology, Faculty of 10 Liu DT, Sabha M, Damm M, et al. Parosmia is The theory behind parosmia, on the Medicine, University of Malaya, Kuala Lumpur, Wilayah associated with relevant olfactory recovery after other hand, is attributed to the unique Persekutuan, Malaysia; shakthy_​ ​18@yahoo.​ ​com olfactory training. Laryngoscope 2021;131:618–23.

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