| anosmia: the condition of having no sense of smell or being unable to smell certain things

During the course of this year, the loss of smell or taste has become associated with the diagnosis of COVID-19, though it has not yet been formally recognized as a symptom. Although symptoms such as having a sore throat or a runny nose have been confirmed as diagnostic criteria for COVID-19, these more common symptoms typically overlap with the symptoms of a minor cold. This can make it difficult to distinguish between a common cold and a case of COVID-19. 

The sense of smell is governed by the olfactory system, which includes the nasal cavity, the optic nerves located at the base of the brain, and the olfactory cortex (the part of the brain that processes information related to the sense of smell). It begins with miniscule particles freely travelling in the air known as odor molecules. During inhalation, these molecules enter through the nostrils and bind to receptor cells at the top of our nasal cavity. The receptors cells then project to the olfactory nerve and relay information to the brain for processing. 

SARS-CoV-2 virus particles follow this same pathway. Because there is no boundary between air and the nasal cavity, the olfactory system is particularly vulnerable to viruses such as COVID-19 which invade the respiratory system. The virus specifically binds to a class of receptors called angiotensin-converting enzyme 2, or ACE-2 receptors

Sandeep Robert Datta, an associate professor of neurobiology at Blavatnik Institute at Harvard Medical School explained, “Our findings indicate that the novel coronavirus changes the sense of smell in patients not by directly infecting neurons but by affecting the function of supporting cells.” 

Though ACE-2 receptor proteins can be found all throughout the body, they are highly concentrated in the nasal cavity and are expressed primarily in two types of supporting cells: sustentacular cells and basal cells. This makes these two types of supporting cells the primary binding targets and entrance to human cells for SARS-CoV-2. Under normal conditions, sustentacular cells provide structural and metabolic support while basal cells aid in regeneration of olfactory epithelium (where olfactory sensory neurons reside) following damage. Temporary loss of function in these supporting cells inadvertently affects performance and regeneration of olfactory sensory neurons, thus impinging upon sense of smell.

Although COVID-19 induced anosmia, or loss of smell, is usually temporary, understanding more about the mechanism behind anosmia is important in accelerating the rate of COVID-19 diagnoses. Kevin Jiang, a writer and editor at Harvard Medical School, states that COVID-19 patients are 27 times more likely to experience loss of smell but are only 2.2 to 2.6 times more likely to experience fever or respiratory symptoms in comparison to patients without COVID-19. For those who are considered asymptomatic outside loss of smell, understanding how to identify a COVID-19 linked case of anosmia can be critical in becoming more proactive in the treatment of a fatal disease. 

Even within this compartmentalization of symptoms for anosmia, there lies variations amongst populations that can provide further clues for rapid diagnosis. A study comparing rates of anosmia between participants from Wuhan, China and Europe has shown that patients’ races influence their chances of experiencing anosmia as a symptom of COVID-19. 

European countries tended to have reported anosmia rates above 50%, while in China, anosmia rates were below 10%. Researchers suggested that different allele frequencies expressed in East Asian populations resulted in an ACE-2 polymorphism, or a difference in phenotype. In the particular case of the ACE-2 receptor, the polymorphism alters the structure of the protein in a way where the receptors have reduced binding affinity. This leads to a lower likelihood of the ACE-2 receptor proteins binding SARS-CoV-2.

 In an attempt to minimize collateral damage of anosmia from the virus, three doctors from the Hadassah Hebrew-University Medical Center in Jerusalem Israel have proposed the use of nasal lavage as a method of minimizing spread of the virus to the rest of the body. Nasal lavage is a procedure typically used for hygienic purposes, in which the nasal cavity is rinsed with a special solution. In the case of COVID-19, the solution would contain an agonist for the ACE-2 receptor which would act as a placeholder, binding in place of where the SARS-CoV-2 virus would typically bind, thus preventing the virus from binding and infecting the cell. By decreasing the likelihood of SARS-CoV-2 binding, it attempts to halt the spread of the virus in its early stages.

Ultimately, a better understanding of anosmia’s link to COVID-19 has strong implications for increasingly efficient diagnosis methods across various populations. In the context of the pandemic where time is a valuable factor in containing transmission of the virus, having a more distinct symptom allows frontline workers as well as lay people to swiftly and reliably identify a case of COVID-19.

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