Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

Absolutely! Although loss of smell was a cardinal symptom of Covid-19 with earlier strains of SARS-CoV-2 (eg, Wuhan, alpha, delta), on average omicron causes olfactory dysfunction in only 13% of patients, 3-4 times lower than the earlier strains.1

But why is omicron less likely to causes loss of smell or taste? There may be at least 2 explanations. First explanation revolves around the solubility of omicron in the olfactory mucus. Recall that to access the olfactory epithelium, viruses and other pathogens have to first dissolve in and penetrate the mucus layer that not only allows odorants to reach the olfactory receptors but also protects the olfactory epithelium from toxins and pathogens. Hydrophilic and acid proteins can penetrate the mucus barrier more easily because they are more soluble in the mucus layer.1

What does this have to do with omicron? Well, it turns out that omicron with all its mutations in the spike protein is actually more alkaline than the Wuhan and delta strains. This means that omicron may have lower solubility in mucus and have a harder time reaching and infecting the olfactory epithelium. 1 Since the composition of olfactory mucous differs significantly from other mucus layers in the respiratory tract, omicron may still cause disease.2

Another potential mechanism may be related to the inefficiency of omicron in other steps necessary to infect nonneuronal cells of the olfactory epithelium within the nasal cavity, such as the endosomal route. 1 It turns out that cells of the olfactory epithelium express less of the endosomal membrane fusion proteases (cathepsins) which omicron prefers for cell entry! Fascinating! 

Bonus Pearl: Did you know that only 5-10% of functional olfactory neurons are required for a relatively normal sense of smell? This means that SARS-CoV-2 needs to eliminate at least 90% of all support cells of the olfactory neurons within a 3-4 day period (before their regeneration) for the host to notice anosmia?

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References

  1. Butowt R, Bilinska K, von Bartheld C. Why does the omicron variant largely spare olfactory function? Implications for the pathogenesis of anosmia in coronavirus disease 2019. J Infect Dis 2022;226:1304-1308. Why Does the Omicron Variant Largely Spare Olfactory Function? Implications for the Pathogenesis of Anosmia in Coronavirus Disease 2019 – PubMed (nih.gov)
  2. Yoshikawa K, Wang H, Jaen C, et al. The human olfactory cleft mucus proteome and its age-related changes. Sci Rep 2018;8:17170. The human olfactory cleft mucus proteome and its age-related changes – PMC (nih.gov)
  3. Harding JW, Getchell TV, Margolis FL. Degeneration of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZNS04 irrigation on behavior, biochemistry and morphology. Brain Res 1978;140:271-85. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology – PubMed (nih.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?