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Tissue damage and shrinkage in brain areas related to smell were seen months after people had mild SARS-CoV-2 infection, longitudinal data from the U.K. Biobank showed.

Compared with controls, people who had mild COVID demonstrated a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus, and greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex, reported Gwenaëlle Douaud, PhD, of the University of Oxford in England, and co-authors in .

COVID patients also had a greater reduction in global brain size. On average, infected participants showed larger cognitive decline.

"Using the U.K. 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," Douaud said in a statement.

"Despite the infection being mild for 96% 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," she noted. "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."

"This is an outstanding study," observed Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, who wasn't involved with the research.

"A novel aspect of this study is the access to MRI scans prior to COVID-19 and then on average 140 days after COVID-19," Nath told 名媛直播. "They show that the olfactory pathways in the brain are atrophic in these patients as a group. This also includes areas involved in cognition although, interestingly, it was an area in the cerebellum."

"These findings might have major implications since it is unlikely they will reverse on their own after so many months," he added. "The critical question is whether this can result in an acceleration of the neurodegenerative process, since the researchers also noted global atrophy."

Douaud and colleagues looked at brain changes in 785 participants 51 to 81 years old who had two MRI scans an average of 3.2 years apart.

A total of 401 participants tested positive for SARS-CoV-2 infection between their scans, including 15 people who were hospitalized. People developed COVID between March 2020 and April 2021; they had a mean age of 58.9 at their first MRI and 62.1 at their second. The other 384 participants were age- and sex-matched controls.

Changes associated with SARS-CoV-2 infection varied in different brain regions but on average, infected participants showed an additional 0.2% to 2% loss compared with non-infected participants, with the largest differences seen in the volume of the parahippocampal gyrus (-1.3%) and entorhinal cortex (-1.8%).

To provide context, these percentages can be compared with the loss seen in -- "for instance, the longitudinal loss per year of ~0.2% (in middle age) to 0.3% (in older age) of hippocampal volume in community-dwelling individuals" -- the researchers noted.

"Our statistics also represent an average effect; not every infected participant will display brain longitudinal abnormalities," they emphasized.

Infected participants took significantly longer to complete complex tasks than non-infected participants, a difference that was more pronounced at older ages. These findings remained significant when excluding the 15 hospitalized cases. There were no signs of memory impairment.

No other brain imaging study has compared scans before and after infection from other viruses, Douaud and co-authors pointed out. A control analysis on 11 people in the U.K. Biobank who developed pneumonia not related to COVID-19 suggested the brain changes were specific to COVID-19 and not generic effects of respiratory illness.

The study had several limitations, the researchers acknowledged. There was no information about COVID symptoms, including smell or taste loss. There also was no formal way to determine which SARS-CoV-2 strain was involved, though the cohort was infected when the original strain and Alpha variant were dominant.

The brain imaging results may be hallmarks of a degenerative spread of SARS-CoV-2 through olfactory pathways, of neuroinflammation, or of a lack of sensory input due to loss of smell, Douaud and co-authors suggested. "Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up," they wrote.

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