Loss of smell is a recurring and long-term symptom associated with COVID-19, significantly impacting a person's quality of life by making it extremely difficult to taste foods and detect airborne hazards in the environment. While the devastating effects of smell loss resulting from COVID-19 are well-known, the underlying biological mechanisms remain somewhat unclear.
In a study published the day before yesterday in the journal "JAMA Neurology," a research team led by Johns Hopkins University found that loss of smell is likely a secondary result of inflammation occurring when the immune system responds to the coronavirus infection, rather than a direct effect of the virus. During the study, Cheng Ying Ho, an associate professor of pathology at Johns Hopkins, and his colleagues collected tissue samples from the olfactory bulb at the base of the brain—an area that transmits nerve impulses carrying smell information—from 23 individuals who died from COVID-19 and a control group of 14 others who died from unrelated causes and showed no detectable coronavirus infection at the time of death.
All tissue samples were evaluated for any detectable viral particles, and using both light and electron microscopy, information about the sense of smell and taste was obtained from clinical records of three patients and family interviews for the remaining patients.
The three patients exhibited signs of loss of smell, and from family interviews, the researchers identified that four others had a reduced ability to smell, while two lost both taste and smell. None of the 14 patients in the control group were identified as having lost their sense of smell or taste.
The researchers aimed to learn three things from their study of the two groups: the levels of degeneration (damage) to the neurons in the olfactory system, the amount of olfactory axon loss, and the severity of microvascular pathology (small vessel disease). What they found was unexpected, as explained by Cheng Ying Ho. He stated, "When we compared tissue from the uninfected patients with tissue from individuals who had contracted the coronavirus, particularly those with significant smell loss or dysfunction, we found that the COVID-19 group showed severe vascular injury and significantly fewer axons in the olfactory bulb. This did not change when we statistically controlled for age effects, strongly suggesting that these effects are not age-related and thus associated with the viral infection."
However, Cheng Ying noted that researchers were surprised by another key finding: despite the neural and vascular damage, viral particles were not detected in the olfactory bulbs of the majority of infected patients. Previous studies, which relied only on routine pathological examinations of the tissues rather than the in-depth analyses that were conducted, suggested that viral infection of the olfactory neurons and bulb may play a role in COVID-19-related smell loss. However, their results indicate that the virus's 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 results in dysfunction in the olfactory bulb.
The researchers plan to conduct a follow-up study on tissues obtained from patients who died due to the Omicron and Delta variants.
