Long COVID Smell Loss is Linked to Changes in Brain Activity

Long COVID anosmia shows different patterns of activity in certain regions of the brain. This may impair communication between brain regions that are related to the sense of smell.

Highlights:

Long COVID smell loss is linked to a change in the brain that impairs communication between two parts of the brain which process important smell information
The majority of people whose sense of smell comes back after long COVID do not have permanent changes to brain activity
Olfactory training, retraining the brain to process different scents, could help people with long COVID recover their sense of smell

A new study led by researchers at University College London (UCL) have found that people living with long COVID who suffer from loss of smell exhibit different patterns of activity in certain regions of the brain. The study used magnetic resonance imaging (MRI) scanning to compare the brain activity of people with long COVID who lost their sense of smell, those whose sense of smell had returned to normal after COVID infection, and people who had never tested positive for COVID-19.

The observational study, which was published in eClinicalMedicine, found that people with long COVID smell loss had reduced brain activity and impaired communication between two parts of the brain that process important smell information: the orbito-frontal cortex and the pre-frontal cortex. This connection was not impaired in people who had regained their sense of smell after COVID ().

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‘Patients with COVID-19-related anosmia have reduced brain activity in regions involved in olfactory processing. This MRI finding suggests that changes in brain function may underlie this symptom. However, if the sense of smell returns, no permanent changes are visible in the MRI.’

The findings suggest that the anosmia caused by long COVID is linked to a change in the brain that stops smells from being processed properly. However, because it is clinically reversible, as shown in some subjects, it may be possible to retrain the brain to recover its sense of smell in people suffering from the side effects of long COVID.

Several studies have shown that a significant proportion of COVID-19 patients experience smell and taste disorders, with estimates ranging from 5% to 85%. Some studies have also reported that these symptoms may persist after the acute phase of the disease, in what is now known as "post-acute sequelae of SARS-CoV-2 infection" or "long COVID."

Supporting Evidence from Similar Studies

A recent study published in JAMA Network Open in March 2022 investigated the prevalence and risk factors for persistent smell and taste dysfunction in patients with mild to moderate COVID-19. The study found that 31.3% of patients reported persistent smell or taste dysfunction at 6 months after infection. The study also identified several risk factors associated with persistent dysfunction, including older age, female sex, and more severe COVID-19 illness ().

Another study published in the Journal of Neurology in January 2022 investigated the brain activity of patients with post-acute sequelae of SARS-CoV-2 infection and persistent smell and taste disorders. The study used functional MRI to compare brain activity in patients with COVID-19-related anosmia, patients with idiopathic anosmia (loss of smell of unknown cause), and healthy controls. The study found that patients with COVID-19-related anosmia had reduced activity in several brain regions involved in olfactory processing, compared to healthy controls and patients with idiopathic anosmia ().

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Dr Jed Wingrove, lead author of the study and a researcher in the UCL Department of Medicine, said: “Persistent loss of smell is just one way long COVID is still impacting people’s quality of life – smell is something we take for granted, but it guides us in lots of ways and is closely tied to our overall well-being. Our study gives reassurance that, for the majority of people whose sense of smell comes back, there are no permanent changes to brain activity.”

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Joint senior author Professor Claudia Wheeler-Kingshott, from the UCL Queen Square Institute of Neurology, added: “Our findings highlight the impact COVID-19 is having on brain function. They raise the intriguing possibility that olfactory training – that is, retraining the brain to process different scents – could help the brain to recover lost pathways, and help people with long COVID recover their sense of smell.”

The study’s authors say their findings also suggest that the brains of people with long COVID smell loss might be compensating for this lost sense by boosting connections with other sensory regions. Their brains had increased activity between the parts of the brain that process smell and areas that process sight (the visual cortex). “This tells us that the neurons that would normally process smell are still there, but they’re just working in a different way,” said Dr. Wingrove.

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Professor Rachel Batterham from the UCL Division of Medicine, who is also a joint senior author of the study, said: “This is the first study to our knowledge that looks at how brain activity changes in people with long COVID smell loss. It builds on the work we undertook during the first wave of the pandemic, which was one of the first to describe the link between COVID-19 infection with both loss of smell and taste.”

The study was funded by the National Institute for Health and Care Research (NIHR).

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References:

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study - (https://pubmed.ncbi.nlm.nih.gov/36883140/)
Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials - (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2804102)
The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237541/)

Source-Medindia