New clues from MRI on lingering smell loss after COVID-19
Researchers have used diffusion tensor imaging (DTI) to explore how the brain’s smell-related circuits change in people who continue to struggle with olfactory dysfunction (OD) months after a mild COVID-19 infection. The study, published in Scientific Reports, focused on non-hospitalized individuals to minimize confounding factors related to severe disease or intensive treatment. The goal was to understand whether lingering OD is associated with structural changes in white matter pathways that connect key odor-processing regions.
Who participated and how the study was done
The study drew participants from the COVIDOM cohort, including 61 adults who had confirmed SARS-CoV-2 infection at least six months earlier. Sixty-three percent were women, and the average age was in the mid-40s. Olfactory function was assessed with the Sniffin’ Sticks test, producing a threshold-discrimination-identification (TDI) score. Individuals with a TDI score below 31 were classified as having post-COVID olfactory dysfunction (PC-OlfDys). Those with preserved smell served as post-COVID normosmic (PC-N) controls.
Beyond smell testing, researchers collected demographic, medical history, and mental-health data, including PHQ-8 (depression) and GAD-7 (anxiety). Cognition was screened using the Montreal Cognitive Assessment (MoCA). Diffusion-weighted MRI provided metrics such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). The team used tract-based spatial statistics (TBSS) for whole-brain analyses and region-of-interest (ROI) analyses to identify subtle, region-specific differences in olfactory-related brain networks.
Key findings: brain regions implicated in persistent OD
Overall, whole-brain TBSS did not reveal significant differences after correcting for multiple comparisons. However, ROI analyses uncovered notable changes in the brains of participants with PC-OlfDys. Specifically, the left amygdala showed higher FA values, and the right amygdala exhibited increased RD values in the PC-OlfDys group compared with controls. These markers hint at microstructural changes in white matter that may reflect adaptive rewiring or myelin alterations in odor-related circuits.
Other regions examined—such as the piriform cortex and putamen—also showed diffusion changes, though the most consistent differences centered on the amygdala, a brain area integral to emotion processing and the integration of sensory cues. Clinically, a sizable portion of PC-OlfDys participants (about 38%) reported parosmia, or distorted smells, during or after infection, while controls reported no such changes.
What the numbers tell us about smell and mood
In the PC-OlfDys group, average PHQ-8 (depression) and GAD-7 (anxiety) scores were higher than in the control group, suggesting a link between persistent OD and emotional well-being. Yet, MoCA scores did not differ significantly, indicating that general cognitive function remained similar between groups in this sample. Importantly, correlations emerged: certain olfactory subtest scores (threshold, discrimination, identification) related to diffusion measures in the anterior piriform cortex, left amygdala, and right putamen, hinting at complex interactions between odor perception and brain microstructure.
Furthermore, the duration of OD after infection correlated with some diffusion metrics in the left amygdala and related olfactory regions, suggesting that longer-lasting smell loss may be linked to greater white matter alterations. These findings support a view that the brain undergoes adaptive changes in olfactory circuits in response to persistent OD, rather than straightforward degeneration.
Implications and cautions for interpreting the data
The researchers emphasize that DTI changes are not direct proof of neurodegeneration. Instead, they may reflect plasticity within olfactory networks as the brain compensates for reduced or distorted sensory input. The link between OD and mood symptoms—anxiety and depression—raises the possibility of bidirectional effects: ongoing smell loss could influence affect, or preexisting mood factors could modulate olfactory perception. Disentangling cause and effect will require longitudinal work with larger samples and complementary imaging approaches.
Why this matters for long COVID care
Understanding how post-COVID OD relates to brain structure helps explain why some individuals experience persistent sensory symptoms and mood changes long after infection. The study’s region-focused approach highlights that interventions aiming to support olfactory rehabilitation might also consider emotional health, given the amygdala’s central role in emotion and smell integration. Clinicians may benefit from monitoring olfactory function alongside mental health in patients reporting long-term OD after COVID-19, enabling more holistic management strategies.
In sum
For people with lingering smell loss after mild COVID-19, MRI findings reveal subtle yet meaningful changes in key olfactory and emotional brain networks, particularly the amygdala. While not proving cause, these results illuminate the brain’s adaptive response to persistent olfactory dysfunction and its potential ties to mood symptoms, offering a path forward for research and care in the era of long COVID.
