How Some COVID-19 Patients Lose Their Sense of Smell

An international team of researchers led by neuroscientists at Harvard Medical School has identified the olfactory cell types most vulnerable to infection by SARS-CoV-2. The temporary loss of smell, or anosmia, is the main neurological symptom and one of the earliest and most commonly reported indicators of COVID-19.

Studies suggest anosmia better predicts the disease than other well-known symptoms such as fever and cough. In fact, analyses of electronic health records indicate that COVID-19 patients are 27 times more likely to have loss of smell, but are only around 2.2 to 2.6 times more likely to have fever, cough or respiratory difficulty, compared to patients without COVID-19.

Their findings were reported in the publication, Science Advances.

The investigators discovered that olfactory sensory neurons do not express the gene that encodes the ACE2 receptor protein, which SARS-CoV-2 uses to enter human cells. Instead, ACE2 is expressed in cells that provide metabolic and structural support to olfactory sensory neurons, as well as certain populations of stem cells and blood vessel cells.

Their findings suggest that infection of nonneuronal supporting cells in the nose and forebrain may be responsible for loss of smell in patients with COVID-19.

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

Some studies have hinted that anosmia in COVID-19 differs from anosmia caused by other viral infections, including by other coronaviruses.

For example, COVID-19 patients typically recover their sense of smell over the course of weeks--much faster than the months it can take to recover from anosmia caused by a subset of viral infections known to directly damage olfactory sensory neurons. In addition, many viruses cause temporary loss of smell by triggering upper respiratory issues such as stuffy nose. Some COVID-19 patients, however, experience anosmia without any nasal obstruction

Some studies are starting to show that some patients who recover from COVID-19 report they have lingering symptoms including anosmia.

However, Datta says the virus is unlikely to damage olfactory neural circuits permanently and lead to persistent anosmia.

"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," he said. "But we need more data and a better understanding of the underlying mechanisms to confirm this conclusion."

Persistent anosmia has been associated with a variety of mental and social health issues, particularly depression and anxiety.