On Mar. 7, 2022, researchers from the University of Oxford have used data from UK Biobank participants to look at changes to the brain on average 4.5 months after mild SARS-CoV-2 infection. The findings, published in Nature, revealed tissue damage and greater shrinkage in brain areas related to smell.

Research has already shown that COVID-19 may cause brain-related abnormalities, but most studies have focused on hospitalized patients with severe disease, and have been limited to post-infection data. The effects of SARS-CoV-2 on the brain in milder (and more common) cases were unknown until now, and investigating these cases could reveal possible mechanisms that contribute to brain disease or damage.

Professor Gwenaëlle Douaud and colleagues investigated changes in the brains of 785 participants in UK Biobank, a large-scale biomedical database and research resource. Participants were aged 51–81 and underwent two brain scans, on average 38 months apart, as well as cognitive tests. A total of 401 participants tested positive for infection with SARS-CoV-2 between their two scans, of whom 15 were hospitalised. The remaining 384 individuals, who did not get infected, were similar to the infected group in age, sex, and many risk factors, including blood pressure, obesity, smoking, socio-economic status and diabetes.

The study, led by the Wellcome Centre for Integrative Neuroimaging at the University of Oxford, identified a number of effects, on average 4.5 months following infection, including a greater reduction in grey matter thickness in the regions of the brain associated with smell (the orbitofrontal cortex and parahippocampal gyrus). UK Biobank participants who had COVID-19 also displayed evidence of greater tissue damage in regions connected with the primary olfactory cortex, an area linked to smell, and a reduction in whole brain size. These effects ranged from 0.2 to 2% additional change compared with the participants who had not been infected.

On average, the participants who were infected with SARS-CoV-2 also showed greater cognitive decline between their two scans, associated with the atrophy of a specific part of the cerebellum (a brain structure) linked to cognition. Separately, the authors studied people who developed pneumonia not related to COVID-19, showing that the changes were specific to COVID-19, and not due to the generic effects of contracting a respiratory illness.