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Even mild cases of COVID-19 are associated with brain changes including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers write.
The findings were published online today in the journal Nature.
Gray Matter Loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK.
They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans to image distinct regions of the brain and brain function.
Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula — all of which are largely involved in the sense of smell.
Participants who had contracted COVID also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More Research Needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ ” Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release.
“The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Taquet has collaborated previously with some of the investigators.
Nature. Published online March 8, 2022. Abstract