Anosmia is the loss of the sense of smell – and since the start of the pandemic, it has been one of the main known symptoms of COVID-19. The reason behind this mechanism is unknown… until now, that is.

The lack of smell is very vexing and frustrating to a lot of people who have had COVID-19, and the path to recovery can take a long time.

“Fortunately, many people who have an altered sense of smell during the acute phase of viral infection will recover smell within the next one to two weeks, but some do not,” said author Bradley Goldstein in a statement, “We need to better understand why this subset of people will go on to have persistent smell loss for months to years after being infected with SARS-CoV2.”

Researchers have found that there is an ongoing immune assault on olfactory nerve cells, and this is associated with a decline in the cells.

This study took olfactory epithelial (the tissue in the nose where the smell nerve cells are located) samples from 24 biopsies, nine from people that had long-term smell loss. 

"Early in the pandemic, it was difficult to get this sort of research involving patients and nasal biopsies up and running; a lot of the initial studies relied on autopsy samples. Also, it was not clear if smell loss would really recover in everyone or not; unfortunately, we have had no shortage of patients presenting with lasting smell loss after Covid-19. While there are some technical challenges with biopsies and with the live single cell approaches we used here, our lab had previously worked out many of these issues." Goldstein told IFLScience. 

Single-cell RNA sequencing and immunohistochemistry were conducted on the samples. It was found the nine smell-loss samples contained fewer olfactory sensory neurons than the controls. This reduction may have been because of damage to the tissue from ongoing inflammation.

"We did include some “never-Covid” controls with normal olfaction and some “post-Covid” controls with normal olfaction, and they do appear similar. So, our impression is that recovered patients either did not lose many neurons, or the repair process indeed replaced most or all of the neurons properly. We do know from prior research (see Durante et al, Nature Neurosci 2020) that under normal conditions the adult human olfactory area in the nose retains the ability to replace damaged neurons, so this would make sense unless there is ongoing inflammation (as we found in post-Covid hyposmics) or such severe damage that the repair mechanisms were overwhelmed." Goldstein told IFLScience. 

Also, the results revealed that there was a widespread infiltration of T-cells engaged in the inflammatory epithelium.

“The findings are striking,” Goldstein said. “It’s almost resembling a sort of autoimmune-like process in the nose.”

“We are hopeful that modulating the abnormal immune response or repair processes within the nose of these patients could help to at least partially restore a sense of smell,” Goldstein said, noting this work is currently underway in his lab.

Despite the small sample size, the research outcomes seem promising, and the mechanisms behind the lack of smell could also explain other long COVID-19 symptoms, such as brain fog, generalized fatigue, and shortness of breath.

"There are a lot of interesting questions to follow up on. For instance, now that we have some understanding of the nature of the problems in long-Covid smell loss, we can begin to test possible drug treatments targeted at these specific problems." Goldstein told IFLScience. 

This work was published in the Science Translational Medicine.