The literature on loss of smell associated with COVID-19 suggests that people in whom these symptoms persist long-term could be at risk for future neurological conditions, according to a rapid review by a collaborative multidisciplinary team of world-renown medical experts that included physicians from the Air Force Research Laboratory (AFRL) and Walter Reed National Military Medical Center. The authors called for new olfactory testing strategies to better understand these persistent symptoms and their potential long-term neurological effects.
"Mounting evidence implicates neuroinflammatory signalling within the brain as a key driver of neurodegenerative diseases. Brain regions involved in processing olfactory input are early sites of the pathological hallmarks of neurodegenerative disease and connect to adjacent brain regions involved in memory and attention," the authors wrote. "We thus postulate that, in people who have recovered from COVID-19, a chronic or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term."
Col. (Dr.) Michael Xydakis, an AFRL otolaryngologist, was the corresponding author on the article, which was published July 30 in The Lancet Neurology.
“Because loss of smell was so common with COVID-19, we knew we needed to analyze and distill the data so that providers could begin to track patients whose smell never came back and then monitor their neurological symptoms,” Xydakis said.
Xydakis offered an analogy as a way to better understand the manner in which olfactory function , which is essentially controlled by memory and attention centers in the brain, may be affected by the virus that causes COVID-19.
“The brain is fundamentally an electrical organ,” Xydakis explained. “So in that regard, think about the cable box hooked to your television. If lightning strikes it during a storm, in most cases, the box will short circuit, turn off and then reboot itself. In some cases, however, due to the age of the box or wiring, it comes back on but has a glitch. As a result, the picture on your television set appears distorted. People who lost their sense of smell and it never came back—their systems didn’t reboot properly. In this case, the lightning is the SARS-CoV-2 virus which is aggressively attacking the olfactory smell receptor high up in the nose – a structure that is just one neuronal synapse away from the brain.”
This research is just the beginning, and suggests a potential risk of neurological problems in the near or distant future.
“Little is known about whether neurons and neuronal networks in the brain that survive a period of excessive stimulation due to neuroinflammation from this virus remain persistently dysfunctional or can completely repair themselves over time,” he said.
The authors could not speculate about what those future problems might be, but Xydakis said that what’s important is that a person whose loss of smell never recovered should be tracked by a physician. He also emphasized a need for the development of additional olfactory testing.
“With this research, there is now great potential and need to develop additional tests. As it stands, what is needed is population-level scalable testing strategies that can monitor the symptoms of this specific subset of people who were infected with COVID-19 and whose smell never returned," Xydakis said. "That’s the data needed next. We don’t have that yet and can’t study it yet because the virus is too new.”
The Lancet Neurology is recognized as a global and authoritative forum for neurological diseases research and opinion.
“AFRL has robust national and international partnerships,” Xydakis said. “For this research, a blue-ribbon panel, invited by The Lancet, quickly came together in hopes of not just furthering the research, but to save lives. This was an all-hands-on-deck effort.”
Read the study: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00182-4/fulltext#%20