Understanding the link between persistent smell loss and brain changes after COVID-19
Researchers have identified measurable changes in brain regions tied to emotion and sensory processing in people who continue to experience a loss or distortion of smell long after a SARS-CoV-2 infection. The study, published in Scientific Reports, used advanced MRI techniques to investigate how olfactory-related brain networks reorganize in individuals with post-COVID olfactory dysfunction (OD).
Study design: who was studied and how?
The study focused on 61 individuals from the COVIDOM cohort to minimize confounding factors related to severe disease or hospitalization. All participants had confirmed SARS-CoV-2 infection at least six months prior. The researchers compared 31 people with persistent OD (PC-OlfDys) to 30 individuals with normal olfactory function (PC-N) after infection. Olfactory function was assessed with the Sniffin’ Sticks test, and the threshold-discrimination-identification (TDI) score was calculated from its subtests.
In addition to smell function, participants completed questionnaires evaluating mood and cognitive status, including the PHQ-8 for depressive symptoms and the GAD-7 for anxiety. Global cognitive function was screened with the Montreal Cognitive Assessment (MoCA).
What imaging and analyses revealed
Diffusion tensor imaging (DTI) was used to assess white matter integrity, focusing on olfactory-related brain regions. Tract-based spatial statistics (TBSS) examined whole-brain diffusion metrics such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Region-of-interest (ROI) analyses allowed for more precise comparisons in key sites like the amygdala and piriform cortex.
Although whole-brain TBSS did not show significant differences after correction for multiple comparisons, ROI analyses uncovered meaningful, region-specific differences. Notably, the left amygdala showed higher FA values in the PC-OlfDys group, while the right amygdala exhibited higher RD values compared with controls. These changes hint at microstructural reorganization in olfactory circuits rather than outright neurodegeneration.
Connections to mood and smell perception
Beyond structural findings, the study observed important correlations between diffusion metrics and olfactory performance. In the OD group, scores on the identification, discrimination, and threshold subtests of the TDI related to diffusion metrics in the anterior piriform cortex, left amygdala, and right putamen. This suggests that the brain’s odor-processing network and emotional centers may adapt in parallel with persistent smell disturbances.
There were also notable links between mood symptoms and brain microstructure. PHQ-8 and GAD-7 scores in the PC-OlfDys group correlated with diffusion properties in the left putamen and left amygdala, implying a potential bidirectional relationship between persistent olfactory loss and emotional well-being. Yet causality remains unclear, and the study emphasizes that diffusion changes should be interpreted as potential adaptive rather than degenerative processes.
Why these findings matter
These results provide a window into how the brain’s olfactory and emotional networks may reorganize after a mild COVID-19 infection. The observed amygdala alterations, coupled with changes in the piriform cortex and putamen, point to a neural basis for both sensory distortion (such as parosmia) and associated anxiety or depressive symptoms often reported by long COVID patients.
Importantly, the study suggests that OD duration correlates with the extent of diffusion changes, reinforcing the idea that longer-lasting smell loss may reflect ongoing neural adaptation within olfactory circuits. While not proof of neurodegeneration, these findings could guide targeted therapies that support olfactory recovery and emotional health.
Takeaway for patients and clinicians
For individuals grappling with persistent smell loss after COVID-19, these findings offer a scientific context for their symptoms and underline the importance of integrated care. Clinicians may consider monitoring mood and cognitive well-being alongside olfactory rehabilitation. Researchers are encouraged to explore longitudinal trajectories to determine whether these brain changes resolve or stabilize over time—and how interventions might influence neural reorganization in olfactory pathways.
Conclusion
The study advances our understanding of long-COVID olfactory dysfunction by highlighting region-specific brain changes, especially in the amygdala, piriform cortex, and putamen. These neural adaptations likely reflect the brain’s attempt to cope with persistent olfactory input and its emotional significance, underscoring the intertwined nature of sense, mood, and brain structure in the aftermath of COVID-19.
