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?

Do statins have a role in treating novel Coronavirus infection, COVID-19?

There is currently no firm clinical evidence that statins improve the outcome of COVID-19. However, there are some theoretical reasons for believing that statins may have a role in the treatment of COVID-19.  That’s because beyond their cholesterol lowering action, statins may also have clinically relevant anti-inflammatory and antiviral (pleotropic) properties.  

Anti-inflammatory: Anti-inflammatory effect of statins is well known and is thought to occur through a variety of molecular pathways of the innate and adaptive immune systems as well as attenuation of several circulating proinflammatory cytokines.1 Although observational studies have suggested that statins lower hospitalization and mortality among outpatients hospitalized with infection, pneumonia or sepsis, several randomized controlled trials (RCTs) have failed to show any mortality benefit among ICU patients with sepsis and ARDS treated with statins.2

In contrast, an RCT involving patients with sepsis (majority with pneumonia, mean CRP 195 mg/dL) reported significant reduction in progression to severe sepsis among statin-naïve patients  placed on atorvastatin 40 mg/day at the time of hospitalization.3 So, perhaps timing of statin therapy before florid sepsis and ARDS is an important factor.  

Some have suggested that statins may decrease the fatality rate of a related Coronavirus, Middle East Respiratory Syndrome (MERS) virus, by blunting exuberant inflammatory response that may result in a fatal outcome. 4

Antiviral: Statins may also have antiviral properties, including activity against influenza, hepatitis C virus, Zika and dengue viruses.2,5 Whether statins have activity against coronaviruses such as the agent of COVID-19 is unclear at this time.

It’s interesting to note that cholesterol may have an important role in the membrane attachment, fusion and replication of many enveloped viruses, including influenza.5 Covid-19 is also an enveloped virus.

So what do we do? Based on the current data, it makes sense to continue statins in patients who have known clinical indications for their use and no obvious contraindications because of COVID-19 (eg. rhabdomyolysis).6 As for statin-naïve patients, particularly those in early stages of sepsis and increased risk of cardiovascular events, benefit may outweigh the risk.  Only proper clinical studies will give us more definitive answers.

Bonus Pearl: Did you know that lipids make up a major component of the envelope in enveloped viruses and that cholesterol makes up nearly one-half of total lipid and over 10% the total mass of influenza viruses?

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References

  1. Tousoulis D, Psarros C, Demosthenous M, et al. Innate and adaptive inflammation as a therapeutic target in vascular diseae: The emerging role of statins. J Am Coll Cardiol 2014;63:2491-2502. https://www.sciencedirect.com/science/article/pii/S0735109714011553?via%3Dihub
  2. Fedson DS. Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola. Ann Transl Med 2016;4:421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124618/pdf/atm-04-21-421.pdf
  3. Patel JM, Snaith C, Thickette DR. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial) Critical Care 2012;16:R231. https://ccforum.biomedcentral.com/track/pdf/10.1186/cc11895
  4. Espano E, Nam JH, Song EJ, et al. Lipophilic statins inhibit Zika virus production in Vero cells. Scientific Reports 2019;9:11461. https://www.nature.com/articles/s41598-019-47956-1
  5. Sun X, Whittaker GR. Role for influenza virus envelope cholesterol in virus entry and infection. J Virol 2003;77:12543-12551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC262566/
  6. Virani SS. Is there a role for statin therapy in acute viral infections. Am Coll Cardiol March 18, 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/09/is-there-a-role-for-statin-therapy-in-acute-viral-infections-covid-19

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its 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!

Do statins have a role in treating novel Coronavirus infection, COVID-19?