Why do some people infected with COVID-19 lose their smell?

Loss of smell (anosmia) is one of the more unusual, but now widely recognised symptoms of COVID-19 infection.
 
According to data from the UK’s ZOE COVID Study, prior to the emergence of the Omicron strain it was in the top 10 most common symptoms of COVID-19, estimated to affect around 50–60% of adults infected with the virus.
 
It was also reportedly the most predictive symptom of testing positive, but that has since changed with the rapid spread of Omicron, which has seen the prevalence of anosmia decrease to around one in five people who test positive.
 
While the prevalence of anosmia, hyposmia (reduced sense of smell) and dysosmia (altered sense of smell) varies between studies and different strains of the virus, existing research appears to link the prevalence of olfactory dysfunction to milder disease which may explain why it is so common.
 
Now, new research published in Nature Genetics offers another possible genetic explanation.
 
A team from the saliva-based DNA service 23andMe recently analysed surveys and genetic samples collected from more than one million participants from the US and UK, and identified almost 70,000 individuals who self-reported a COVID-19 positive test and anosmia or ageusia (loss of taste) as a result of their infection.
 
When comparing this cohort to individuals with COVID-19 but without anosmia or ageusia, they were able to pinpoint a set of variants located near two specific genes, UGT2A1 and UGT2A2.
 
The presence of these variants increased the likelihood that an individual experienced a loss of taste or smell from COVID-19 infection by 11%.
 
In those who experience anosmia, symptoms usually arise early and suddenly in the disease course, and last an average of five days. For those who experience persistent anosmia post-infection, symptoms typically resolve within six months.
 
Anosmia also appears to occur independently of nasal congestion, although the mechanism underlying the symptom is not yet entirely clear.
 
‘We know that smell loss in COVID-19 is more than the simple mechanism we see with seasonal upper respiratory infections, where common symptoms of nasal congestion and runny nose result in poor airflow and reduced delivery of odours to the region of the nose responsible for smell,’ Dr Jonathan Overdeverst, Assistant Professor of Rhinology and Skull Base Surgery at Columbia University, said.
 
Early research attempting to explain the symptom theorised that the virus infected and damaged olfactory neurons within the nose and brain, but there is now evidence to suggest that COVID-19-related anosmia is the result of the virus acting on non-neuronal cells in the olfactory system.
 
Unlike olfactory neurons, these cells express ACE2, which is known to assist viral entry suggesting a possible mechanism through which the virus causes olfactory dysfunction.
 
In addition, both UGT2A1 and UGT2A2 are normally expressed in the olfactory epithelium and play a role in metabolising and eliminating odorants that bind to receptors involved in smell detection.
 
The research from 23andMe found females were more likely (72%) than males (61%) to report the symptom, as were younger people (mean age of 41 years) and those of European ancestry. 
 
But while the new paper provides further clues into the biological mechanisms that underly COVID-19-related anosmia as well as ageusia, the authors caution several study limitations.
 
Despite the large sample size, the study was biased toward individuals of European ancestry, relied on self-reported case and symptom status, and combined loss of smell and taste into a single survey question.
 
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