The temporary loss of smell that some Covid-19 patients experience may not be as dangerous as generally presumed as a new study led by neuroscientists at Harvard Medical School has found that olfactory support cells, not neurons, are vulnerable to novel coronavirus infection.
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 it better predicts the disease than other well-known symptoms such as fever and cough, but the underlying mechanisms for loss of smell in patients with Covid-19 have been unclear.
The new research, published in the journal Science Advances, identified the olfactory cell types most vulnerable to infection by SARS-CoV-2, the virus that causes Covid-19.
Surprisingly, the sensory neurons that detect and transmit the sense of smell to the brain are not among the vulnerable cell types.
“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 in the Blavatnik Institute at Harvard Medical School.
This implies that in most cases, SARS-CoV-2 infection is unlikely to permanently damage olfactory neural circuits and lead to persistent anosmia, Datta added, a condition that is associated with a variety of mental and social health issues, particularly depression and anxiety.
“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.”
In the current study, Datta and colleagues set out to better understand how sense of smell is altered in Covid-19 patients by pinpointing cell types most vulnerable to SARS-CoV-2 infection.
They began by analysing existing single-cell sequencing datasets that in total catalogued the genes expressed by hundreds of thousands of individual cells in the upper nasal cavities of humans, mice and nonhuman primates.
The research showed 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.
The findings suggest that infection of nonneuronal cell types may be responsible for anosmia in Covid-19 patients and help inform efforts to better understand the progression of the disease.