SARS-CoV-2 is associated with changes in brain structure in UK Biobank
Authors: Rory Collins
Bernd Taschler
Soojin Lee
Gwenaëlle Douaud
Fidel Alfaro-Almagro
Anderson M Winkler
Paul M Matthews
Karla L Miller
Saad Jbabdi
Ludovica Griffanti
Stephen M Smith
Christoph Arthofer
Thomas E Nichols
Peter Keating
Jesper L R Andersson
Frederik Lange
Paul McCarthy
Chaoyue Wang
Naomi Allen
Eugene Duff
Journal: Nature (2022)
Discipline: Multidisciplinary
Keywords: COVID-19; brain abnormalities; SARS-CoV-2 infection; magnetic resonance imaging; longitudinal effects

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. 

Retracted: No

PubPeer comments:
 This article was reviewed on the error bar podcast episode 26: https: theerrorbar.com ?e=26 story 109: https: theerrorbar.com ?s=109. The review was done in the light of newspaper headlines about the article. The slightly-edited transcript is copied here: headline: COVID SHRINKS BRAIN tweet: a large brain scanning study finds that some parts of the brains of older adults shrink after infection mild symptoms of covid. these are small specific changes in the brain, but every percentage counts. avoid covid. description: in a study echoed across lots of news media this week, the Guardian reports that brain scientists from Oxford found that even mild cases of COVID shrinks the brain damages its tissue. [editorial note: the error bar has not cover COVID stories so far, to avoid the inevitable trolling, but this one was too prominent to ignore.] the study relied on the UK s BioBank - a long term research study that has scanned the brains testing the minds bodies of thousands of people. in this specific study, 785 typically-healthy older adults brains were scanned twice. the first scan was done before COVID arrived, the second, an average of 38 months later, which was, coincidentally, four a half months after infection with COVID. the scans revealed that the overall brain size decreased more in those who had COVID that some brain areas linked to smell taste showed larger specific decreases in brain size. perhaps most significant is that these decreases in brain volume were observable even though the volunteers had mostly had mild symptoms, the differences remained when 15 more severe cases were excluded. evaluation: does COVID shrink the brain yes, it seems so. but don t believe all the headlines - it s not as bad as it might sound. first, the study covered a very wide age-range of participants - from 51 to 80 years - but there was much less brain shrinkage in the youngest participants. because of the way the data are presented, it looks like there is a continuous larger decrease in brain size as age increases from 56 to 76, but this depends partly on the authors using a 10-year sliding window to average the data. that means the 56-year-old data includes 51 to 61 year-olds. so it might be that only those over 65 years show brain shrinkage - it s not quite clear. second, it s not the whole brain that is shrinking, but rather several important parts of the brain related, arguably, to smell taste. some brain areas or signals seemed to *increase* in size too. it s not a simple story, but overall there seem to be clear differences between the groups. third, although every bit of brain is important COVID-related brain loss seems to accelerate with age, these are still relatively small changes, occurring in people with only mild illness. the changes may largely reflect what happens when you lose your sense of smell taste. conclusion: this important study shows that, on average, the oldest participants brains were more affected by COVID than the youngest. some brain areas signals got bigger, some smaller. overall, there was a small decrease in brain size after COVID. short conclusion: avoid COVID , 
 They performed a family-wise error correction and 8 out of 250 comparisons were significant. This is less than would be expected by chance alone (meaning, the data do not support their conclusion) -Andrew Rivers https: twitter.com amrivers1 status 1574911247711375360?t=g-BJnoSQZXw2tvGGJM--lw s=19 ,