Affected olfactory support cells responsible for loss of smell in COVID-19
A majority of COVID-19 patients experience a temporary loss of smell, medically termed anosmia. Analyses of health records indicate that COVID-19 patients are 27 times more likely to have some level of anosmia 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. It has been recently implicated that infection of nonneuronal cell types – not sensory neurons that detect and transmit smell – may be responsible for anosmia in COVID-19 patients.
“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 Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS.
Datta and colleagues analysed existing single-cell sequencing datasets that catalogued genes of cells in the upper nasal cavities of humans, mice and nonhuman primates. In particular, they focused on the ACE2 gene, which encodes the main receptor protein that SARS-CoV-2 targets to gain entry into human cells, and the TPRSS2 gene, which encodes an enzyme thought to be important for SARS-CoV-2 entry into the cell.
It was later revealed that both ACE2 and TMPRSS2 are expressed by cells in the olfactory epithelium, a specialised tissue in the roof of the nasal cavity responsible for odour detection. These included sustentacular cells, which wrap around sensory neurons and are thought to provide structural and metabolic support, and basal cells, which act as stem cells that regenerate the olfactory epithelium after damage. Neither gene was expressed by olfactory sensory neurons.
In individual cells of the olfactory bulb, the structure in the forebrain that receives signals from olfactory sensory neurons, the ACE2 gene and its associated protein were present only in blood vessel cells, particularly pericytes, which are involved in blood pressure regulation, blood-brain barrier maintenance and inflammatory responses. No cell types in the olfactory bulb expressed the TMPRSS2 gene.
This implies that SARS-CoV-2 infection, the virus causing COVID-19 disease, is unlikely to permanently damage olfactory neural circuits and lead to persistent anosmia. The findings also suggest and help inform efforts to better understand the progression of COVID-19 which could in turn lead to treatments for anosmia and the development of improved smell-based diagnostics for the disease. “Anosmia seems like a curious phenomenon, but it can be devastating for the small fraction of people in whom it’s persistent,” Datta said. “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.”
