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

Author

Listed:
  • 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
    University of Oxford)

  • Eugene Duff

    (University of Oxford
    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)

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.

Suggested Citation

  • 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 & Be, 2022. "SARS-CoV-2 is associated with changes in brain structure in UK Biobank," Nature, Nature, vol. 604(7907), pages 697-707, April.
    • Handle: RePEc:nat:nature:v:604:y:2022:i:7907:d:10.1038_s41586-022-04569-5
    DOI: 10.1038/s41586-022-04569-5
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    Cited by:

    1. Yirui Ma & Jie Deng & Qiao Liu & Min Du & Min Liu & Jue Liu, 2022. "Long-Term Consequences of COVID-19 at 6 Months and Above: A Systematic Review and Meta-Analysis," IJERPH, MDPI, vol. 19(11), pages 1-16, June.
    2. Pi Alperin, María Noel & Perquin, Magali & Giordana, Gastón A., 2024. "Population ageing and public finance burden of dementia: Micro-simulations evaluating risk factors, treatments and comorbidities in Luxembourg," The Journal of the Economics of Ageing, Elsevier, vol. 28(C).
    3. Carlos Eduardo Covantes-Rosales & Victor Wagner Barajas-Carrillo & Daniel Alberto Girón-Pérez & Gladys Alejandra Toledo-Ibarra & Karina Janice Guadalupe Díaz-Reséndiz & Migdalia Sarahy Navidad-Murriet, 2022. "Comparative Analysis of Age, Sex, and Viral Load in Outpatients during the Four Waves of SARS-CoV-2 in A Mexican Medium-Sized City," IJERPH, MDPI, vol. 19(9), pages 1-9, May.
    4. Cunwei Yang & Weiqing Wang & Fengying Li & Degang Yang, 2022. "One-Size-Fits-All Policies Are Unacceptable: A Sustainable Management and Decision-Making Model for Schools in the Post-COVID-19 Era," IJERPH, MDPI, vol. 19(10), pages 1-21, May.
    5. Caitlin E. Carey & Rebecca Shafee & Robbee Wedow & Amanda Elliott & Duncan S. Palmer & John Compitello & Masahiro Kanai & Liam Abbott & Patrick Schultz & Konrad J. Karczewski & Samuel C. Bryant & Caro, 2024. "Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation," Nature Human Behaviour, Nature, vol. 8(8), pages 1599-1615, August.
    6. Christophe Hausswirth & Cyril Schmit & Yann Rougier & Alexandre Coste, 2023. "Positive Impacts of a Four-Week Neuro-Meditation Program on Cognitive Function in Post-Acute Sequelae of COVID-19 Patients: A Randomized Controlled Trial," IJERPH, MDPI, vol. 20(2), pages 1-16, January.
    7. Samuel Hurtado & Mario Izquierdo, 2023. "Economic effects of a possible prolonged deterioration in the general health of the Spanish population," Economic Bulletin, Banco de España, issue 2023/Q1.
    8. Dominika Tatar & Krzysztof Świerzy & Michał Błachut & Karina Badura Brzoza, 2022. "Psychotic Disorders in the Course of SARS-CoV-2 Infection or Uncomplicated Amantadine Treatment?—Case Report," IJERPH, MDPI, vol. 19(23), pages 1-7, November.

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