SARS-CoV-2 is associated with changes in brain structure in UK Biobank

Gwenaëlle Douaud (), Soojin Lee, Fidel Alfaro-Almagro, Christoph Arthofer, Chaoyue Wang, Paul McCarthy, Frederik Lange, Jesper L. R. Andersson, Ludovica Griffanti, Eugene Duff, Saad Jbabdi, Bernd Taschler, Peter Keating, Anderson M. Winkler, Rory Collins, Paul M. Matthews, Naomi Allen, Karla L. Miller, Thomas E. Nichols and Stephen M. Smith
Additional contact information
Gwenaëlle Douaud: University of Oxford
Soojin Lee: University of Oxford
Fidel Alfaro-Almagro: University of Oxford
Christoph Arthofer: University of Oxford
Chaoyue Wang: University of Oxford
Paul McCarthy: University of Oxford
Frederik Lange: University of Oxford
Jesper L. R. Andersson: University of Oxford
Ludovica Griffanti: University of Oxford
Eugene Duff: University of Oxford
Saad Jbabdi: University of Oxford
Bernd Taschler: University of Oxford
Peter Keating: University College London
Anderson M. Winkler: National Institutes of Health
Rory Collins: University of Oxford
Paul M. Matthews: Imperial College
Naomi Allen: University of Oxford
Karla L. Miller: University of Oxford
Thomas E. Nichols: University of Oxford
Stephen M. Smith: University of Oxford

Nature, 2022, vol. 604, issue 7907, 697-707

Abstract: Abstract There is strong evidence of brain-related abnormalities in COVID-191–13. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days on average separating their diagnosis and the second scan—as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.

Date: 2022
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DOI: 10.1038/s41586-022-04569-5

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