by Dr. Juliette Dufour
For April 2022, we have selected: G. Douaud et al, SARS-CoV-2 is associated with changes in brain structure in UK Biobank, Nature, 2022. https://doi.org/10.1038/s41586-022-04569-5.
There is strong evidence for brain-related pathologies in Covid-19 (by viral neurotropism or virus-induced neuroinflammation) with an incidence of neurological symptoms in more than 80% of the severe cases. The more frequent one being hyposmia (> 80%).
Brain imaging studies revealed a broad array of cerebral abnormalities ranging from white matter hyperintensities, hypoperfusion and signs of ischaemic events spread throughout the brain. However, it remains unknown whether any of these abnormalities predates the infection by SARS-CoV-2. These effects could be associated with a pre-existing increased brain vulnerability to the deleterious effects of COVID-19 and/or a higher probability of showing more pronounced symptoms, rather than being a consequence of the COVID-19 disease process.
Our authors of the month conducted a longitudinal, multi-modal brain imaging study using the UK biobank, whereby participants had already been scanned before getting infected with SARS-CoV-2, offering a unique resource to elucidate these questions.
In total, 785 subjects were enrolled (aged 51-81): 401 SARS-CoV-2 infected patients (positive test between their two scans) and 384 controls matched for age, sex, ethnicity and time elapsed between the two scans.
The authors identified significant longitudinal effects when comparing the two groups, including:
(i) greater reduction in grey matter thickness and tissue-contrast in the left orbitofrontal cortex and parahippocampal gyrus
(ii) greater changes in markers of tissue damage (diffusion measures) in regions functionally-connected to the primary olfactory cortex (piriform cortex, olfactory tubercle and anterior olfactory nucleus)
(iii) greater reduction in global brain size and increase of global CSF volume
The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the cases who had been hospitalized.
This is the first longitudinal imaging study of COVID-19 where subjects were scanned before and after infection. This unique study confirms the impact of Covid-19 in brain imaging, mainly in limbic and olfactory cortical system, beyond any potential baseline differences and risk factors.
The authors, using specialized image processing, detected subtle changes invisible at individual level in brain tissue, offering new perspectives in the comprehension of the neurological effects of COVID-19.
These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. But whether these abnormalities are the hallmark of the spread of the pathogenic effects, or of the virus itself in the brain remains to be investigated.