Temporary loss of smell or anosmia is one of the first identified and among the most common symptoms of COVID-19. An international research team led by neuroscientists at Harvard Medical School, or HMS, has found the reason behind COVID patients temporarily losing their sense of smell.

In the report published in Science Advances on Friday, July 24, researchers found that olfactory sensory neurons (OSN) do not express a specific gene that encodes ACE2. It is the receptor protein through which SARS-CoV-2, the virus that causes COVID-19, enters cells in the human body.

In the report published on the HMS website, the receptor protein is expressed instead in cells providing metabolic and structural support of OSNs. ACE2 was also found in specific populations of stem cells and blood vessel cells.

Olfactory Neurons Don't Need to Be Replaced

These findings suggest that anosmia might be caused by the infection of nonneuronal cell types, instead of olfactory sensory neurons.

"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, senior study author and an associate professor of neurobiology in the Blavatnik Institute at HMS.

Datta added that their findings imply, in most cases, a SARS-CoV-2 infection is unlikely to cause permanent damage to olfactory neural circuits and persistent anosmia. Extended cases of loss of smell, the neurobiologist added, are associated with mental and social health conditions, such as depression and anxiety.

RELATED: New Study Proposes Causal Link Between Loss Of Smell And Memory Problems

"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," Datta said. However, the HMS neurobiologist admitted to needing "more data and a better understanding of the underlying mechanisms to confirm this conclusion."

Tracing CoV-2 Entry Genes

The research team poured through previously-published RNA-Seq from the whole olfactory mucosa (WOM) from macaques, marmoset, and humans. All CoV-entry-related genes were found in all WOM samples. Further verification was done by studying data from mice, verifying that ACE2 and other genes related to CoV-2 entry are expressed in the olfactory epithelium.

Researchers then quantified gene expressions in scSeq taken from four human nasal biopsy samples from an earlier study published in Nature Neuroscience last February. The gene expressions quantified yielded no presence of ACE2 and TMPRSS2, another gene relevant to the entry of SARS-CoV-2 into human cells. However, both genes were found in sustentacular cells and horizontal basal cells (HBC). Sustentacular cells wrap around sensory neurons, provide structural and metabolic support, and also aid in the regeneration of the olfactory epithelium after damage.

Additional tests also revealed that after injury, ACE2 and TMPRSS2 are expressed in subsets of sustentacular cells and HBCs, with the activated HBC expressing ACE2 at higher levels compared to its resting counterparts.

Anosmia: One of the Earliest SARS-CoV-2 Indicators

Temporary loss of smell or anosmia is among the most commonly reported indicators for COVID-19. Compared to other reported symptoms such as cough or fever, studies suggest that anosmia is a more reliable indicator.

RELATED: Loss of Smell and Taste: Peculiar Signs of COVID-19 

Last April 13, researchers from the University of California - San Diego have established empirical findings strongly linking sensory loss, such as anosmia, to COVID-19. The UCSD team surveyed 1,480 patients exhibiting flu-like symptoms. In the sample, 102 individuals later tested positive for the novel coronavirus. Carol Yan, MD, explained that among the COVID-19 positive patients, more than 70 percent reported improvement in the sense of smell at the time of the survey.

A research study published in medRXiv last May 24 explores the effect of SARS-CoV-2 toward chemosensory impairment - loss of smell, as well as taste and chemosthesis. A survey included in the report illustrated an average loss of almost 80 percent for normal smell function, 69 percent in taste, and 39 percent in normal chemesthetic functions.