Published: July 22, 2022

Pearls from Your Peers

COVID-19-related olfactory dysfunction

August Pearls Zacharek Stanley 85What is the prevalence of COVID-19-related olfactory dysfunction?

Approximately 50% of patients with COVID-19 infection experience some degree of olfactory dysfunction. The prevalence of anosmia, hyposmia, parosmia, phantosmia, hypogeusia, and dysgeusia is so high that the American Academy of Otolaryngology–Head and Neck Surgery advocated for these symptoms to be included in the screening for COVID-19 as early as March 2020. In July 2020 the Centers for Disease Control and Prevention added olfactory dysfunction to the list of presenting symptoms for this infection.

Olfactory dysfunction is more commonly experienced by women, individuals < 50 years of age, and those with a milder clinical course not requiring hospitalization. It has been shown to have a significant effect on quality of life and social interactions and is associated with an increased rate of depression. There are also safety considerations for patients with severe olfactory dysfunction. The use of both smoke and natural gas detectors is critical for those who live or work alone. In addition, food safety is a concern, and a “food taster” is often recommended to avoid ingestion of potentially rotten or toxic food substances.

What are the mechanisms for olfactory dysfunction following SARS-CoV-2 infection?

It is well established that SARS-CoV-2 enters cells through angiotensin converting enzyme (ACE) receptors on the cell surface. Nasal and oral tissues are typically the first sites exposed to this virus. There are at least two plausible explanations for olfactory dysfunction in patients with COVID-19. First, short-term mucosal edema may inhibit the flow of odorants to the olfactory cleft. This is sometimes referred to as “olfactory cleft syndrome.” Second, the virus itself may cause injury and death of cells in the olfactory region. This includes injury to sustentacular cells, supporting cells that harbor the greatest number of ACE receptors, Bowman’s glands, which reside beneath the olfactory epithelium and olfactory basal cells. This phenomenon is frequently referred to as “post-viral anosmia syndrome” and has been reported with other types of viral infection.

It appears that ACE receptors on sustentacular cells are the primary target of the SARS-CoV-2 spike protein and may result in cell death. Sustentacular cells contain two important genes, UGT2A1 and UGT2A2, which are responsible for metabolizing and detoxifying odorants. Olfactory epithelial basal cells may be injured by the body’s innate cytokine and interleukin immune response. Fortunately, these cells may retain the ability to regenerate, which accounts for the high rate of recovery of olfactory function following COVID-19 infection. Severe loss of these primordial olfactory basal cells may account for the permanent loss of olfaction observed in a small subset of patients.

What is the natural history of this condition?

Over 80% of patients have return of olfactory function at six months and over 90% at 12 months. Only 5%-10% of patients have persistent olfactory symptoms beyond one year, presumably caused by the permanent loss of olfactory epithelial basal cells.

What type of evaluation and testing is recommended?

A careful history confirming the temporal relationship to COVID-19 infection and ruling out other known causes—e.g., head trauma and other potential causes—is the first step in evaluation of this condition. Next, objective testing using smell tests may be useful to determine the degree of dysfunction and assist in patient counseling. The University of Pennsylvania Smell Identification Test (UPSIT) is a commonly used assessment tool to measure an individual’s ability to detect odors at a suprathreshold level and takes only a few minutes to complete in the clinic. Imaging studies are rarely indicated.

What treatment options are available?

Although there have been no randomized placebo-controlled trials, treatment with topical steroids with or without oral steroids may be useful to decrease inflammation within the olfactory cleft during the acute phase of infection. In addition, the regular use of nasal saline rinses is recommended. Finally, olfactory training using central odorants may be helpful by stimulating olfactory epithelium inducing transmembrane protein changes with induction of greater receptor numbers and ultimately nerve regrowth.

What is on the horizon regarding the treatment of this condition?

There are studies underway investigating the use of intranasal sodium citrate to reduce free calcium and the use of intranasal platelet-rich plasma and intranasal insulin to reduce inflammation and promote regrowth of neuroepithelial tissue in patients with olfactory dysfunction following COVID-19 infection.

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