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Brain imaging before and after COVID-19 in UK Biobank

Our take —

This study, available as a preprint and thus not yet peer-reviewed, included 394 patients with COVID-19 and 388 individually-matched controls, and evaluated brain imaging data from the UK Biobank collected prior to the COVID-19 pandemic and follow-up scans from February-June 2021. Of 297 hypothesis-driven imaging derived phenotypes (IDPs) and 2,022 exploratory IDPs, most longitudinal differences between the groups were in regions of the brain related to olfactory and gustatory systems, as well as some related to memory function, which are consistent with some of the common symptoms of COVID-19. Results may be limited by residual confounding and it’s not yet clear whether these are acute and reversible or longer-lasting changes due to COVID-19.

Study design

Case-Control, Retrospective Cohort

Study population and setting

This was an ambidirectional cohort study, leveraging existing imagining data from the UK Biobank imaging study, which had completed 42,729 brain scans before the COVID-19 pandemic and included follow-up imaging data on 798 participants after the beginning of the COVID-19 pandemic (782 of whom had usable data and 394 of whom had COVID-19 between visits). The follow-up imaging study included people who had a COVID-19 diagnosis based on primary care data, hospital records, antigen tests linked through the Public Health datasets in England, or two concordant positive home-based lateral flow kits, and a group of controls from the remaining UK Biobank imaging participants who didn’t have a history of COVID-19 and were individually matched by age, ethnicity, date of birth (+/- 6 months), location of imaging assessment, and date of first imaging assessment (+/- 6 months). 2,260 brain imaging-derived phenotypes were used to describe different aspects of brain structure and function, based on three structural MRI scans (T1, T2 fluid attenuation inversion recovery, and susceptibility weighted MRI) as well as diffusion MRI, resting MRI, and task MRI. The analysis focused primarily on analyzing 332 pre-specified brain regions of interest based on expectations from animal models and post-mortem findings, including those related primarily to olfactory and gustatory function. Beyond that, the full set of imaging derived phenotypes were explored. All analyses were focused on longitudinal differences, considering the difference in imaging between scans (adjusted for baseline function) and were adjusted for multiple comparisons.

Summary of Main Findings

The final study population included 394 patients who had COVID-19 (median age 59.1 years, 57% female) and 388 controls (median age 60.4 years, 57% female), all of whom had imaging prior to and during the COVID-19 pandemic (average time between scans was 3.1 years for both groups). Only 15 of the participants with COVID-19 were hospitalized during their infection. Of 297 olfactory and gustatory regions that passed quality assurance tests, only 8 showed significant differences between groups after adjusting for multiple comparisons. These included reduced grey matter thickness or volume over time in the primary or secondary cortical gustatory and olfactory areas in the left hemisphere in the COVID-19 patients compared to controls. In the exploratory analysis of 2,022 imaging derived phenotypes that passed initial quality checks, the longitudinal difference for COVID-19 cases vs. controls was only significant for four measures: patients with COVID-19 had more prominent reductions the ratio of brain volume to total intracranial volume, reductions in cortical thickness of the parahippocampal gyrus and lateral orbitofrontal cortex, as well as increases in lateral ventricle volume. Many of these changes are linked to memory or olfactory function.

Study Strengths

Brain imaging data was available from prior to the COVID-19 pandemic and during the COVID-19 pandemic. Controls were individually matched to COVID-19 cases based on several important characteristics.


Follow-up imaging data during the COVID-19 pandemic were only available for a subset of the people originally evaluated in the UK Biobank imaging study. It is not clear how the COVID-19 cases or controls were selected for follow-up. They had limited power to evaluate differences in imaging between hospitalized and non-hospitalized COVID-19 patients. Despite matching and considering baseline differences, residual confounding, due to clinical comorbidities or other factors is still possible. It is not clear whether the observed changes are a long-term consequence of infection that will persist over time or if they are a more acute manifestation of COVID-19 that will resolve.

Value added

This is the first study that includes comprehensive brain imaging data on COVID-19 patients and control from before and during the COVID-19 pandemic.

This review was posted on: 30 July 2021