People living with long-term Covid who suffer from loss of smell show different patterns of activity in certain regions of the brain, a new study led by UCL researchers has found.
Functional Connectivity of the Aberrant Olfactory Network in People with Olfactory Dysfunction After COVID-19 Infection: An Exploratory Observational Study Background Olfactory deficiencies and anosmia from COVID-19 infection typically resolve within 2 to 4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. Methods In this exploratory observational study, we studied people who experienced COVID-19-related anosmia, with or without a recovered sense of smell, and compared them to people without prior COVID-19 infection (confirmed by antibody testing, all without vaccine). MRI was carried out between 15 July and 17 November 2020 at Queen Square House Clinical Examination Centre, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole-brain gray matter (GM), cerebral blood flow (CBF), and GM density . Results Individuals with anosmia showed increased functional connectivity (FC) between the left orbitofrontal cortex (OFC), visual association cortex, and cerebellum and reductions in FC between the right OFC and dorsal anterior cingulate cortex compared to those without infection. previous COVID-19 (p < 0.05, whole-brain statistical analysis of parametric maps). Individuals with anosmia also showed increased cerebral blood flow (CBF) in the left insula, hippocampus, and ventral posterior cingulate cortex compared to those with resolved anosmia (p < 0.05, from analysis of statistical parametric maps of the whole brain). Interpretation This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for future research and potential target sites for therapeutic strategies. |
Anatomical image showing the location of the bilateral seeds used for connectivity analysis, which comprises the olfactory network. In green the orbitofrontal cortex (OFC), in blue the anterior insula (AI) and in red the Piriform Cortex (Pir). The groups were defined based on the coordinates of Tobia et al. Each seed is 9 mm in diameter.
Comments
The research used magnetic resonance imaging 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.
Published in eClinicalMedicine , the observational study found that people with long-term loss of smell from Covid had reduced brain activity and impaired communication between two parts of the brain that process important information about smell: the orbitofrontal cortex and the prefrontal cortex. This connection was not affected in people who had recovered their sense of smell after Covid.
The findings suggest that the loss of smell, known as anosmia, caused by long Covid is linked to a change in the brain that prevents odors from being processed properly. Because it is clinically reversible, as shown in some subjects, it is possible to retrain the brain to regain its sense of smell in people suffering from the side effects of long Covid.
Dr Jed Wingrove (UCL Department of Medicine), lead author of the study, said: "Persistent loss of smell is just one of the ways in which Covid continues to affect people’s quality of life - smell is "Something we take for granted, but it guides us in many ways and is closely linked to our overall well-being. Our study ensures that, for the majority of people whose sense of smell returns, there are no permanent changes in brain activity."
Joint lead author Professor Claudia Wheeler-Kingshott (UCL Queen Square Institute of Neurology) said: “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 smells – could help the brain recover lost pathways and help people with long Covid regain their sense of smell.”
The researchers say their findings also suggest that the brains of people with long-term smell loss from Covid could be compensating for this lost sense by boosting connections with other sensory regions: Their brains had greater activity between the parts of the brain that process smell. smell and the areas that process vision. (the visual cortex).
"This tells us that the neurons that would normally process odor are still there, but they work in a different way," Dr. Wingrove said.
Professor Rachel Batterham (UCL Division of Medicine), also joint lead author of the study, said: “This is the first study we know of that looks at how brain activity changes in people with long-term loss of smell from Covid. “It is based on the work we did during the first wave of the pandemic, which was one of the first to describe the link between Covid-19 infection with the loss of smell and taste.”
Added value of this study
These data show that there are functional connectivity changes in secondary odor processing regions as well as regions involved in cognitive processing as a result of long-lasting COVID anosmia compared to healthy controls (not exposed to COVID-19). 19). Additionally, we identified brain perfusion differences within olfactory regions between people who regain their sense of smell and those still suffering from long-COVID anosmia.
Implications of all available evidence
Our data highlight the impact of COVID-19 anosmia on functional brain connectivity and cerebral perfusion. These data open potential avenues for treatments and ways to measure the success of olfactory training for those still suffering from long COVID-19.
The study was funded by the National Institute for Health and Care Research (NIHR).
