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More Data on SARS-CoV-2 and Structural Brain Changes

The study covered in this summary was published in as a preprint and has not yet been peer reviewed.

Key Takeaways

  • This study explores the effects of mild to moderate COVID-19 over the long haul, focusing on brain-related pathologies.

  • To the authors’ knowledge, this is the first longitudinal study of SARS-CoV-2 in which individuals underwent initial imaging before any had contracted the virus. The longitudinal analyses showed a substantial, deleterious impact associated with SARS-CoV-2.

  • A consistent clinical feature, which can manifest before the onset of respiratory symptoms, is the disruption of smell and taste in COVID-19 patients. The loss of sensory olfactory inputs to the brain could result in a loss of gray matter in brain regions regulating those functions.

Why This Matters

  • Strong evidence supports the existence of brain-related abnormalities in patients with COVID-19. Yet, before this study, it remained unknown whether the impact of SARS-CoV-2 infection could be identified in milder cases. It was also unclear whether this could uncover possible mechanisms that play a role in brain pathology.

  • The overlapping olfactory- and memory-related functions of the brain regions that appear to change significantly over time in SARS-CoV-2, including the parahippocampal gyrus/perirhinal cortex, entorhinal cortex, and hippocampus in particular, indicate that longer-term consequences of SARS-CoV-2 infection may contribute to Alzheimer’s disease or other types of dementia.

Study Design

  • The researchers investigated brain alterations in 785 UK Biobank participants. The patients ranged in age from 51 to 81 years and underwent imaging twice. There were 384 control patients and 401 case patients who tested positive for infection with SARS-CoV-2 between their two scans. There was an average of 141 days between their diagnosis and the second scan.

  • The availability of preinfection imaging data decreases the possibility that preexisting risk factors could be misinterpreted as disease effects.

Key Results

  • The investigators noted major longitudinal effects in comparing the two groups, including higher reduction in gray matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus, more significant changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex, and greater reduction in global brain size.

  • Infected participants also demonstrated on average more significant cognitive decline between the two time points.

  • These imaging and cognitive longitudinal effects were still evident after exclusion of the 15 hospitalized patients.

  • These primarily limbic brain imaging findings may be the in vivo hallmarks of a degenerative proliferation of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input attributed to anosmia.

  • Additional studies are needed to evaluate whether these deleterious effects can be partially reversed or whether these effects will persist in the long term.


  • There was a lack of stratification of cases beyond the information of whether individuals had been hospitalized (information on O2 saturation levels and details of treatment or hospital procedures are currently available on only a few participants).

  • There was also a lack of clinical correlates, inasmuch as they are not currently available as part of the UK Biobank COVID-19-related links to health records (of particular relevance, potential hyposmic and hypogeusic symptoms and blood-based markers of inflammation).

  • The researchers lacked knowledge of the particular SARS-CoV-2 strain that infected each participant.

  • There was a small number of participants from Asian, Black or other ethnic backgrounds other than White.

  • SARS-CoV-2 infection status for some of the case patients and controls was identified through antibody lateral flow test kits that differ in diagnostic accuracy.

Study Disclosures

  • The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “SARS-CoV-2 Is Associated With Changes in Brain Structurein UK Biobank,” written by GwenaĆ«lle Douaud, from the University of Oxford, published on medRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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