June 15, 2021 ~ MedRxiv ~ Gwenaëlle Douaud et al.

Brain imaging before and after COVID-19 in UK Biobank

Abstract
There is strong evidence for brain-related pathologies in COVID-19, some of which could be a
consequence of viral neurotropism. The vast majority of brain imaging studies so far have
focused on qualitative, gross pathology of moderate to severe cases, often carried out on
hospitalised patients. It remains unknown however whether the impact of COVID-19 can be
detected in milder cases, in a quantitative and automated manner, and whether this can
reveal a possible mechanism for the spread of the disease. UK Biobank scanned over 40,000
participants before the start of the COVID-19 pandemic, making it possible to invite back in
2021 hundreds of previously-imaged participants for a second imaging visit. Here, we studied
the effects of the disease in the brain using multimodal data from 782 participants from the
UK Biobank COVID-19 re-imaging study, with 394 participants having tested positive for SARSCoV-2 infection between their two scans. We used structural and functional brain scans from
before and after infection, to compare longitudinal brain changes between these 394 COVID19 patients and 388 controls who were matched for age, sex, ethnicity and interval between
scans. We identified significant effects of COVID-19 in the brain with a loss of grey matter in
the left parahippocampal gyrus, the left lateral orbitofrontal cortex and the left insula. When
looking over the entire cortical surface, these results extended to the anterior cingulate
cortex, supramarginal gyrus and temporal pole. We further compared COVID-19 patients who
had been hospitalised (n=15) with those who had not (n=379), and while results were not
significant, we found comparatively similar findings to the COVID-19 vs control group
comparison, with, in addition, a greater loss of grey matter in the cingulate cortex, central
nucleus of the amygdala and hippocampal cornu ammonis (all |Z|>3). Our findings thus
consistently relate to loss of grey matter in limbic cortical areas directly linked to the primary
olfactory and gustatory system. Unlike in post hoc disease studies, the availability of preinfection imaging data helps avoid the danger of pre-existing risk factors or clinical conditions
being mis-interpreted as disease effects. Since a possible entry point of the virus to the central
nervous system might be via the olfactory mucosa and the olfactory bulb, these brain imaging
results might be the in vivo hallmark of the spread of the disease (or the virus itself) via
olfactory and gustatory pathways.

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