text: Brain imaging before and after COVID 19 in UK Biobank 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 SARS CoV 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 COVID 19 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 i post hoc i disease studies the availability of pre infection 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 i in vivo i hallmark of the spread of the disease or the virus itself via olfactory and gustatory pathways 