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.
Highlights
401 SARS-CoV-2 infected participants with usable imaging data at both timepoints were included in this study, as well as 384 controls, matched for age, sex, ethnicity and time elapsed between the two scans
We found that significant longitudinal differences remained in the same set of significant brain regions surviving FDR or FWE correction when removing from the SARS-CoV-2 group those patients who had been hospitalised with COVID-19 (Model 2, 47 IDPs FDR-significant, 3 of which FWE-significant, Supplementary Table 1)
Our longitudinal analyses revealed a significant, deleterious impact associated with SARS-CoV-2
Summary
Gwenaëlle Douaud1 ✉, Soojin Lee[1], Fidel Alfaro-Almagro[1], Christoph Arthofer[1], Chaoyue Wang[1], Paul McCarthy[1], Frederik Lange[1], Jesper L. 401 SARS-CoV-2 infected participants with usable imaging data at both timepoints were included in this study, as well as 384 controls, matched for age, sex, ethnicity and time elapsed between the two scans These large numbers may allow us to detect subtle, but consistent spatially distributed sites of damage associated with the infection, underlining in vivo the possible spreading pathways of the effects of the disease within the brain Through hospital records available for participants, we identified 15 of the SARS-CoV-2 positive group who were hospitalised with COVID-19, including 2 who received critical care (Tables 2 and 3) These hospitalised patients were on average older, had higher blood pressure and weight, and were more likely to have diabetes and to be men, compared with non-hospitalised cases (Table 3). We found significant longitudinal effects trast over time in the cases compared with controls
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