While brain-related abnormalities have been observed in cases of severe Covid-19, a new study suggests that even a mild infection can result in tissue damage and greater shrinkage in brain areas related to smell.

Researchers from the University of Oxford looked at changes to the brains of 785 people, aged 51-81, on average of 4.5 months after mild SARS-CoV-2 infection.

The study, published in the journal Nature, identified a number of effects, including a greater reduction in grey matter thickness in the regions of the brain associated with smell (the orbitofrontal cortex and parahippocampal gyrus).

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 percent additional change compared with the participants who had not been infected.

These findings may be the hallmarks of the degenerative spread of Covid, either via pathways related to the sense of smell, inflammation or immune response of the nervous system, or a lack of sensory input owing to a loss of smell.

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"Despite the infection being mild for 96 percent of our participants, we saw a greater loss of grey matter volume and greater tissue damage in the infected participants," said lead author Professor Gwenaelle Douaud, from the varsity.

The participants also underwent two brain scans, on average 38 months apart, as well as cognitive tests, before being infected with SARS-CoV-2, and also after infection.

On average, the participants who were infected with SARS-CoV-2 also showed a greater cognitive decline between their two scans, associated with the atrophy of a specific part of the cerebellum (a brain structure) linked to cognition.

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Separately, the team studied people who developed pneumonia not related to Covid, showing that the changes were specific to Covid, and not due to the generic effects of contracting a respiratory illness.

The participants "also showed a greater decline in their mental abilities to perform complex tasks, and this mental worsening was partly related to these brain abnormalities," Douaud said.

Importantly, all these negative effects were more marked at older ages.

Whether these effects persist in the long term or are partially reversed, requires further investigation, Douaud said.