by 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.97, 100 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. The inflammatory pathways induced by SARS-CoV-2 in the nasal epithelium overlap substantially with inflammatory signalling described in subsets of patients with dementia.55, 101 An inflammatory stimulus from the nasal epithelium to the olfactory bulbs and connected brain regions might, therefore, accelerate pathological processes and progression of neurodegenerative disease. Although the prevalence of inflammatory signalling in the olfactory bulbs of patients with COVID-19 is unknown, robust inflammation in the nasal olfactory epithelium (as seen in SARS-CoV-2 infections) can propagate sterile inflammation to the olfactory bulbs in animal models.101 Survivors of COVID-19, with or without persistent olfactory impairment, might be at risk of accelerated onset or progression of neurodegenerative disease and should be studied longitudinally with imaging and molecular biomarkers, and cognitive profiling, to test this postulated risk. Additionally, as vaccination efforts reduce mortality, they will also exert an enduring impact on morbidity by decreasing the neurological sequelae of SARS-CoV-2.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8324113
Alterations of the amygdala in post-COVID olfactory dysfunction
In conclusion, this study highlights significant brain changes associated with persistent olfactory dysfunction (OD) following SARS-CoV-2 infection. Using DTI, we identified alterations in key olfactory-related brain regions, particularly in the amygdala, putamen and piriform cortex, where increased fractional anisotropy and radial diffusivity values suggest both enhanced myelination and potential disruptions in white matter integrity. Our findings also suggest that the longer the OD persists after the infection, the greater the DTI changes within critical olfactory circuits. This may have implications for both olfactory function and mental health outcomes. The observed correlations between diffusion metrics, olfactory scores, and depression/anxiety assessments (PHQ-8 and GAD-7) underscore the complex relationship between prolonged OD and its psychological impact.
Our results add to the growing body of evidence that links post COVID-19 condition with cerebral changes, particularly in olfactory processing regions, and suggests that these alterations may be drivers of persistent symptoms. Future longitudinal studies with larger cohorts and potentially further subcohorts are necessary to further elucidate the trajectory of recovery and the potential for structural and functional brain changes to serve as biomarkers for persistent OD and associated mental health conditions.
