ACE2 polymorphism: studies suggest that East Asian populations possess different allele frequencies of ACE2 than European populations, and that some ACE2 variants may have reduced ability to bind SARS-Cov1. Depending on which ACE2 type patients with COVID-19 have in different tissues, they may experience vastly different symptoms and outcomes in recovery.


Syracuse University

Anosmia and ageusia have been widely reported in COVID-19 patients in Italy, especially in younger patients. Out of 417 patients with mild to moderate COVID-19 in Milan, Italy, 85.6% reported olfactory dysfunction, and from 202 patients with mild COVID-19 symptoms in another hospital in Italy, 64.4% had impaired sense of smell or taste.
In Wuhan, China, among 214 patients hospitalized for COVID-19 symptoms, only 5.1% and 5.6% had impaired smell or taste, with impairment more prevalent among patients with mild rather than severe COVID-19 (6-7% versus 3.0%).


Reported Cases of Anosmia and Ageusia in COVID-19 Patients 

Fotuhi, M., Mian, A., Meysami, S., & Raji, C. A. (2020). Neurobiology of COVID-19. Journal of Alzheimers Disease, 76(1), 3-19. doi:10.3233/jad-200581
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200581

Neurobiology of COVID-19

Hypothesis for Significant Difference in Reported Anosmia or Ageusia between East Asia and European Communities

There has been speculation about the potential causes of anosmia and ageusia in COVID-19 patients. Two key MOAs have been proposed: a neuronal infection-based hypothesis and a non-neuronal infection-based hypothesis.

Potential Causes of Anosmia and Ageusia in COVID-19 Patients

Anosmia recovery rates in patients affected by COVID-19 is typically several weeks. However, other viral infections typically cause anosmia for months. This difference might be due to the lack of olfactory inflammation in some COVID-19 cases that is usually observed with other virus cases (including other coronaviruses).

Comparison of COVID-19-Related Anosmia and Other Viral-Related Anosmia 

- Anosmia is a result of congestion or the presence of edema in the nasal area
- When volunteers were vaccinated with a strain of the coronavirus, they experience nasal obstruction
- Due to infection, inflammation was presented in olfactory tissue. This then resulted in edema and rhinorrhea
- Further study on the nasal tissue found that there was a diminished cilia count and less olfactory neurons present (which could be an indicator of the inability to smell)
- Unlike the use of ACE2 in COVID-19 for the virus to bind to receptors on cells, the inoculation strain (HCoV-229E) uses aminopeptidase N
- Those with COVID-19 showed that the presence of increased amounts of ACE2 resulted in damaged cilia and goblet cells in the nasal tissue 
- In a survey done on patients with anosmia in South Korea, it was found that 30% of them had anosmia
- Out of 214 patients in Wuhan, 11 of them had anosmia
- An inoculation of a different strain of the coronavirus in mice through the nasal cavity showed that the virus could be detected in the olfactory bulb after 3 days
- Cytokines were present in the olfactory bulb
- COVID-19 could eventually spread to the blood-brain barrier would disrupt homeostasis in the brain, negatively impacting the olfactory area


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