The loss of smell due to COVID would be a consequence of nerve inflammation and not the virus

Anosmia, that is, the loss of smell, is a frequent and often long-term symptom associated with COVID-19 that can seriously affect a person's quality of life, making it very difficult to taste food, detecting airborne hazards in the environment and the performance of other sense-dependent functions.

While the devastating impacts of COVID-mediated anosmia are well known, the biological mechanisms underlying the condition remain a mystery. In a study published in JAMA Neurology, a team led by Johns Hopkins Medicine demonstrated that loss of smell is probably a secondary consequence of inflammation that occurs when the system immune system of the body responds to infection with SARS-CoV-2 rather than a direct action of the virus.

“As a neuropathologist, I wondered why loss of smell is a very common symptom of COVID-19 but not of other respiratory diseases,” commented the study's lead author, Cheng-Ying Ho, an associate professor of pathology at Johns Hopkins University School of Medicine. So, we decided to delve into the mechanics of smell to see what really happens at the cellular level when SARS-CoV-2 invades the body.”

To conduct their research, Ho and colleagues collected tissues from the olfactory bulb at the base of the brain, a region that transmits nerve impulses that transmit information about odors, from 23 people who died from COVID-19 and a control group of 14 who died from other causes and that they had no detectable SARS-CoV-2 at the time of their death.

All tissues were evaluated for detectable SARS-CoV-2 particles; the structure and characteristics of cells, blood vessels, and neurons (nerve cells) within them, using light and electron microscopy; and the number of axons (the portions of neurons that transmit electrical impulses) present. Information on smell and taste was obtained from the medical records of three patients and from family interviews for the rest.

Three of the 23 COVID-19 patients were found to have lost their sense of smell, four had a diminished ability to smell, and two had loss of both smell and taste. None of the 14 patients in the control group were identified as having lost smell or taste. The researchers wanted to learn three things from their study of the two groups: the levels of degeneration (damage) of neurons in the olfactory system, the number of olfactory axons lost, and the severity of microvasculopathy (disease of the small blood vessels). What they found, according to Ho, was not unexpected.

“When we compared the tissues of patients without COVID-19 with those of people who had been infected with SARS-CoV-2, especially those who had a total or decreased loss of smell, we found that the group with COVID showed a more severe vascular lesion and far fewer axons in the olfactory bulb,” says Ho. And that did not change when we statistically controlled the impact of age, which strongly suggests that these effects are not age-related and therefore linked to SARS-CoV-2 infection.”

However, the researcher assured that they were surprised by the other important finding of the study: that, despite nerve and vascular damage, SARS-CoV-2 particles were not detected in the olfactory bulb in most patients with COVID-19.

“Previous research that was only based on routine pathological examinations of the tissue, and not on the deep, ultra-fine analyses we performed, assumed that viral infection of olfactory neurons and olfactory bulb could play a role in the loss of smell associated with COVID-19,” he adds. But our findings suggest that SARS-CoV-2 infection of the olfactory epithelium leads to inflammation, which in turn damages neurons, reduces the number of axons available to send signals to the brain, and causes the olfactory bulb to become dysfunctional.”

Next, the researchers plan to conduct a follow-up study on tissues taken from patients who died from the Omicron and Delta variants of SARS-CoV-2.

“We want to compare any axonal damage and bulb dysfunction found in those tissues with what we observed in patients who had the original strain of the virus,” Ho concluded. That way, we can better predict whether Delta and Omicron are more or less likely to cause loss of smell.”

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