Covid-19 and loss of smell: Harvard researchers uncover why it happens

  • Anosmia is a common symptom among people with mild Covid-19 
  • New research has uncovered why the virus may cause a temporary loss sense of smell
  • Further observation is, however, needed to confirm the team's findings

Evidence of loss of smell (anosmia) as a symptom of Covid-19 first emerged in late February 2020. In April, the symptom was officially added to the Centers for Diseases Control and Prevention’s list of Covid-19 symptoms. At that stage, however, very little was known about how and why the virus affects an infected person’s sense of smell.

Previous studies suggested that the sensory neurons (which detect and transmit the sense of smell to the brain) were vulnerable cell types, but new research indicates otherwise. An international team of researchers led by neuroscientists at Harvard Medical School (HMS) recently identified the olfactory cell types that are most vulnerable to infection by SARS-CoV-2 (the virus that causes Covid-19).

The results were published in Science Advances

Anosmia mostly temporary in Covid-19 cases

The loss of smell has proven to be one of the most reliable neurological indicators of early infection with the new coronavirus. A previous study published in the journal Clinical Infectious Diseases found that between 25% and 50% of patients report anosmia and ageusia (loss of taste) as the first symptoms of Covid-19. 

Further analysis of global patient records found this symptom to be as likely to predict a SARS-CoV-2 positive PCR (polymerase chain reaction) as a fever, cough, or a stuffy nose. According to the study’s news release, emerging data indicate that the majority of Covid-19 patients experience some level of anosmia, but that it is often only temporary. 

Some studies have also hinted that anosmia in Covid-19 patients differs from anosmia caused by other viral infections, including other coronaviruses. Covid-19 patients, for example, typically recover their sense of smell within a couple of weeks, whereas the condition brought about by other viral infections are known to damage olfactory sensory neurons to the extent that it can take months for people to recover their sense of smell.

Why olfactory sensory neurons are vulnerable

According to the researchers’ results, olfactory sensory neurons don’t express the gene that encodes the ACE2 receptor protein. ACE2 are the receptors (or doors) that allow the virus to enter the body's cells.

Instead, it is the olfactory support cells, not neurons, that are vulnerable to SARS-CoV-2 infection. The discovery that the infection of non-neuronal cell types is potentially responsible for anosmia in Covid-19 patients is therefore helping scientists to better understand the progression of the disease.

Their data suggest that a temporary loss of function of supporting cells in the olfactory epithelium (tissue in the nasal cavity involved in smell), which indirectly causes changes to olfactory sensory neurons, is what may cause Covid-19-related anosmia.

"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," said senior study author Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS, adding:

"We don't fully understand what those changes are yet, however. Sustentacular cells have largely been ignored, and it looks like we need to pay attention to them, similar to how we have a growing appreciation of the critical role that glial cells play in the brain."

Anosmia and mental health conditions

Datta explained that the results imply that in the majority of cases the virus is unlikely to permanently damage a patient’s olfactory neural circuits and lead to persistent anosmia, and added that the condition is often associated with mental and social health issues, such as depression and anxiety. This 2016 study, for example, found that in people with anosmia, symptoms of depression worsened with the severity of olfactory dysfunction.

"I think it's good news, because once the infection clears, olfactory neurons don't appear to need to be replaced or rebuilt from scratch. But we need more data and a better understanding of the underlying mechanisms to confirm this conclusion."

The team now hopes that their results could lead to treatments for the condition, as well as the development of improved smell-based diagnostics for Covid-19.

"Anosmia seems like a curious phenomenon, but it can be devastating for the small fraction of people in whom it's persistent. It can have serious psychological consequences and could be a major public health problem if we have a growing population with permanent loss of smell," said Datta.

Further observations would be more compelling

While the results of the study are advancing the understanding of the link between SARS-CoV-2 and anosmia, former professor at HMS, William A. Haseltine, wrote in Forbes that the results are based on indirect observations:

"Biopsies of infected tissue that show the virus does indeed infect and replicate in sustentacular cells would be more helpful. An observation of both the damage and recovery of the tissue would be even more compelling," he wrote. 

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