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Review
. 2022 Sep;28(9):781-794.
doi: 10.1016/j.molmed.2022.06.005. Epub 2022 Jun 20.

Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health

Richard L Doty  1
Affiliations
Review

Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health

Richard L Doty. Trends Mol Med. 2022 Sep.

Abstract

Decreased smell function is related to brain health, future mortality, and quality of life. Most people inflicted with the SARS-CoV-2 virus evidence some measurable smell dysfunction during its acute phase, although many are unaware of the loss. Long-term deficits occur in up to 30% of COVID-19 cases, although total anosmia is relatively rare. This review explores what is presently known about the nature and pathophysiology of olfactory dysfunction due to the SARS-CoV-2 virus, including reversible inflammation within the olfactory cleft, downregulation of olfactory receptor proteins, and long-lasting peripheral and central damage to olfactory structures. It also addresses the question as to whether long-term smell loss might increase the likelihood of future development of cognitive and neurological deficits.

Keywords: COVID-19; SARS-CoV-2; anosmia; neuropathology; olfaction; taste.

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Conflict of interest statement

Declaration of interests The author is a consultant to Eisai Co, Merck Pharmaceuticals, the Michael J. Fox Foundation for Parkinson's Research, and Johnson & Johnson. He receives royalties from Cambridge University Press, Johns Hopkins University Press, and John Wiley & Sons, and is president of, and a major shareholder in, Sensonics International, a manufacturer and distributor of smell and taste tests.

Figures

Figure 1
Figure 1
Suggested mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus affects the sense of smell. These include local airway inflammation, particularly in the higher recesses of the nose, infection and damage to specific cell types within the olfactory neuroepithelium, over-reactive immune responses within the brain, and downregulation of olfactory receptor proteins located on the cilia of olfactory receptor cells. As a result of viral infection, macrophages are activated, which in turn releases a multitude of cytokines, with interleukin 6 producing the most inflammation. The listed cytokines are examples and not an inclusive list of cytokines that can influence olfactory functioning. Copyright © 2022 Shima Moein. Abbreviations: ACE2, angiotensin-converting enzyme II; TMPRSS2, transmembrane protease serine 2.
Figure 2
Figure 2
Basic anatomy of the nose, olfactory epithelium, and olfactory bulb. Left: Air, including aerosols and odorants, enters into the nasal cavity and a portion reaches the olfactory neuroepithelium located within the olfactory clefts on sectors of the nasal septum and superior and middle turbinates. The highly vascular turbinates warm, cleanse, and filter the air. Right: Olfactory receptor proteins are located on the olfactory cilia. The olfactory neuroepithelium is comprised of multiple cell types, which germinate from basal cells. The axons of the receptor cells extend through the bony cribriform plate to synapse with other cell types in globe-like structures within the olfactory bulb, the first relay station of the olfactory pathway. Copyright © 2022 Shima Moein.
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