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COVID and the Loss of Smell


There are few patient complaints more frustrating to both patients and healthcare providers than the loss of the sense of smell and taste. Usually, both deficits go together and are due to a secondary process in various disease states, or in some cases such as after a COVID infection, it may be a primary symptom. In this article, we will review the loss of smell associated with COVID, the hypotheses about how it happens and what can be done about it.

There are degrees of the loss of smell, and they are classified as “-osmias.” Anosmia is the total loss of smell. Hyposmia is the decreased ability to detect odors. Dysosmia is an altered smell sensation. Many sufferers of COVID experience all the above, particularly phantosmia which means a perception of smell without an odor being present.

How do we smell?

The sense smell originates high up in the nasal cavity in the olfactory neuroepithelium, adjacent to the base of the skull called the cribriform plate. The neural cells are very specialized, and they contain primary olfactory receptors that transmit information through the first cranial nerve to the brain.

The sense of smell is derived through volatile chemicals which stimulate these olfactory nerves. Airborne molecules must traverse through the nose and nasal cavity to reach these nerves, experiencing turbulence and obstruction all the way. Odorants can also come up through the other direction from our nasopharynx, particularly when we are eating or drinking.

Olfactory nerves can number one hundred million or more in an average person. The olfactory nerves are unique because they are generated throughout our lives. New ones can be created approximately every 30-60 days. That fact can be a neurological miracle for most people who lose their sense of smell, particularly from infections such as COVID.

How do we lose our sense of smell?

There are two main pathways that can result in a disturbance of olfaction. It should be pointed out that all of us experience a decrease in our sense of smell as we age.

Conductive causes

  1. Inflammatory causes (Allergic, Acute, Toxic (such as cocaine use)
  2. Infection (Upper respiratory infection, Sinusitis)
  3. Blockage
    1. Masses (nasal polyps, papilloma, and nasal tumor)
    2. Deviated nasal septum
    3. Enlarged nasal lining (turbinates)
    4. Developmental abnormalities (encephaloceles, dermoid cysts)
    5. Those patients who have undergone surgery for laryngeal cancer or children who have had tracheotomies

Central/Sensorineural causes

  1. Infectious and inflammatory processes such as COVID
  2. Head trauma
  3. Brain surgery
  4. Subarachnoid hemorrhage (bleeding in the brain)
  5. Endocrine disturbances such as hypothyroidism and diabetes mellitus
  6. Neurologic diseases such as Parkinson’s
  7. Dementia

How do we lose our sense of smell from COVID infection?

The short answer is that no one really knows for sure. Anyone with a disturbance in their sense of smell for any reason can have a frustrating journey in determining why it has happened and what can be done about it.

I have seen patients ranging from world class chefs to athletes to everyday people who have had the loss of smell even before COVID. The first steps in diagnosis are a thorough history and physical examination to determine if there is an underlying cause.

Clinical measurement of olfaction is time-consuming and complicated. Often these tests such as the butanol threshold test can even be unpleasant. Other tests like the University of Pennsylvania Smell Identification Test can have good reliability, but do not offer too many solutions for patients.

A recent study1 surveyed 616,318 people in the United States who had have COVID. The findings showed that those people who had been infected with the original virus, the Alpha variant, were 50% as likely to have lost their sense of smell. 44% of those with the Delta variant and 17% of those with Omicron had the loss of the sense of smell.

Some people recover their sense of smell over time, but for others the recovery is incomplete, unfortunately. Almost half of patients who have had COVID have some disturbance in their sense of smell even a year later.

The reasoning as to why COVID infections cause the sense smell to diminish involves the hypothesis that the virus attacks the sustentacular cells in the nose. These are the cells that provide nutrients and support the odor-sensing neurons.2 The neurons’ nuclei of the odor-sensing cells become, in a sense, scrambled.

Other theories involve the finding of a genetic mutation in people who have had an association with a tendency to loss of smell with COVID. In one study, there was found to be two overlapping genes UGT2A1 and UGT2A2.3 Both encode proteins that remove odor molecules from the nostrils after they have been detected. But it is not yet clear how COVID interacts with these genes.

What can I do about my loss of smell after COVID?

Many treatments are being explored. Smell testing of strong-smelling substances is often employed to monitor progress and offer small solutions, but these methods tend to help those with only partial loss of smell.

Some researchers are exploring means to reduce inflammation in the olfactory system with steroids. So far, the results of these clinical trials have been unsuccessful.

Others have attempted using platelet-rich plasma from the patient’s own blood to induce healing. A few patients have benefited from this approach.

The best news is to repeat the fact that olfactory neurons are resilient, and they do continue to generate throughout our lives. This means with time, there should be hope even for those who have had COVID anosmia, complete loss of smell.

References

Yale Medicine https://www.yalemedicine.org/news/prevent-loss-smell-covid

Cleveland Clinic https://my.clevelandclinic.org/health/diseases/21859-anosmia-loss-of-sense-of-smell

Mayo Clinic https://www.mayoclinic.org/symptoms/loss-of-smell/basics/definition/sym-20050804

1Coelho DH, Reiter ER, French E, Costanzo RM. Decreasing Incidence of Chemosensory Changes by COVID-19 Variant. Otolaryngol Head Neck Surg. 2022 May 3:1945998221097656. doi: 10.1177/01945998221097656. Epub ahead of print. PMID: 35503739.

2Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou HJ, Fletcher RB, Das D, Street K, de Bezieux HR, Choi YG, Risso D, Dudoit S, Purdom E, Mill J, Hachem RA, Matsunami H, Logan DW, Goldstein BJ, Grubb MS, Ngai J, Datta SR. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020 Jul 31;6(31):eabc5801. doi: 10.1126/sciadv.abc5801. Epub 2020 Jul 24. PMID: 32937591.

3Shelton JF, Shastri AJ, Fletez-Brant K; 23andMe COVID-19 Team, Aslibekyan S, Auton A. The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste. Nat Genet. 2022 Feb;54(2):121-124. doi: 10.1038/s41588-021-00986-w. Epub 2022 Jan 17. PMID: 35039640.

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