Changes to the brain may occur even after a mild case of COVID-19, new research has revealed.
Using UK Biobank data to look at changes an average of 4.5 months after mild SARS-CoV-2 infection, the study revealed tissue damage and greater shrinkage in brain areas related to smell.
Previous studies have already shown that COVID-19 may cause brain-related abnormalities, but most studies have focused on hospitalised 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.
The research, led by the Wellcome Centre for Integrative Neuroimaging at the University of Oxford, has been hailed as adding to overall understanding of how the virus spreads through the central nervous system.
A team led by Professor Gwenaлlle Douaud investigated changes in the brains of 785 participants in UK Biobank. Participants were aged 51 to 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 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 two per cent 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 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.
Prof Douaud said: ‘Using the UK Biobank resource, we were in a unique position to look at changes that took place in the brain following mild—as opposed to more moderate or severe—SARS-CoV-2 infection.
“Despite the infection being mild for 96 per cent of our participants, we saw a greater loss of grey matter volume, and greater tissue damage in the infected participants, on average 4.5 months after infection.
“They also showed greater decline in their mental abilities to perform complex tasks, and this mental worsening was partly related to these brain abnormalities. All these negative effects were more marked at older ages.
“A key question for future brain imaging studies is to see if this brain tissue damage resolves over the longer term.”
Professor Stephen Smith, senior author on the study, also from the Wellcome Centre for Integrative Neuroimaging, said: “Another strength of this study is that it investigated the same people at two different times.
“Importantly here, the first scan of UK Biobank participants was obtained before they became infected with SARS-CoV-2, and the second scan after infection.
“The fact that we have the pre-infection scan helps us distinguish brain changes related to the infection from differences that may have pre-existed in their brains.”
