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February 27, 2023 article Open access Aachen paper

Structural brain changes in patients with post-COVID fatigue: a prospective observational study

EClinicalMedicine, vol. 58, pp. 101874

DOI: 10.1016/j.eclinm.2023.101874 Full text (OA) OpenAlex

Abstract

Background: Post-COVID syndrome is a severe long-term complication of COVID-19. Although fatigue and cognitive complaints are the most prominent symptoms, it is unclear whether they have structural correlates in the brain. We therefore explored the clinical characteristics of post-COVID fatigue, describe associated structural imaging changes, and determine what influences fatigue severity. Methods: We prospectively recruited 50 patients from neurological post-COVID outpatient clinics (age 18-69 years, 39f/8m) and matched non-COVID healthy controls between April 15 and December 31, 2021. Assessments included diffusion and volumetric MR imaging, neuropsychiatric, and cognitive testing. At 7.5 months (median, IQR 6.5-9.2) after the acute SARS-CoV-2 infection, moderate or severe fatigue was identified in 47/50 patients with post-COVID syndrome who were included in the analyses. As a clinical control group, we included 47 matched multiple sclerosis patients with fatigue. Findings: Our diffusion imaging analyses revealed aberrant fractional anisotropy of the thalamus. Diffusion markers correlated with fatigue severity, such as physical fatigue, fatigue-related impairment in everyday life (Bell score) and daytime sleepiness. Moreover, we observed shape deformations and decreased volumes of the left thalamus, putamen, and pallidum. These overlapped with the more extensive subcortical changes in MS and were associated with impaired short-term memory. While fatigue severity was not related to COVID-19 disease courses (6/47 hospitalised, 2/47 with ICU treatment), post-acute sleep quality and depressiveness emerged as associated factors and were accompanied by increased levels of anxiety and daytime sleepiness. Interpretation: Characteristic structural imaging changes of the thalamus and basal ganglia underlie the persistent fatigue experienced by patients with post-COVID syndrome. Evidence for pathological changes to these subcortical motor and cognitive hubs provides a key to the understanding of post-COVID fatigue and related neuropsychiatric complications. Funding: Deutsche Forschungsgemeinschaft (DFG) and German Ministry of Education and Research (BMBF).

Authors 16

  1. Josephine Heine

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  2. Katia Schwichtenberg

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  3. Tim Julian Hartung

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  4. Sophia Rekers

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  5. Claudia Chien

    Max Delbrück Center · Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany

    NeuroCure Clinical Research Center (NCRC), Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany

  6. Fabian Boesl

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  7. Rebekka Rust

    Max Delbrück Center · Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and Max Delbrück Center for Molecular Medicine, Berlin, Germany

  8. Christian Hohenfeld Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

    Jülich Aachen Research Alliance · RWTH Aachen University

    Affiliation as printed

    Department of Neurology, RWTH Aachen University, Aachen, Germany

    JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11), Research Centre Jülich and RWTH Aachen University, Aachen, Germany

  9. Julia Bungenberg Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

    Jülich Aachen Research Alliance · RWTH Aachen University

    Affiliation as printed

    Department of Neurology, RWTH Aachen University, Aachen, Germany

    JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11), Research Centre Jülich and RWTH Aachen University, Aachen, Germany

  10. Ana S.H. Costa Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

    Jülich Aachen Research Alliance · RWTH Aachen University

    Affiliation as printed

    Department of Neurology, RWTH Aachen University, Aachen, Germany

    JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11), Research Centre Jülich and RWTH Aachen University, Aachen, Germany

  11. Carmen Scheibenbogen

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany

    Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany

  12. Judith Bellmann–Strobl

    Max Delbrück Center · Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and Max Delbrück Center for Molecular Medicine, Berlin, Germany

  13. Friedemann Paul

    Max Delbrück Center · Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany

    NeuroCure Clinical Research Center (NCRC), Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany

  14. Christiana Franke

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

  15. Kathrin Reetz Aachen Department of Neurology JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11)

    Jülich Aachen Research Alliance · RWTH Aachen University

    Affiliation as printed

    Department of Neurology, RWTH Aachen University, Aachen, Germany

    JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11), Research Centre Jülich and RWTH Aachen University, Aachen, Germany

  16. Carsten Finke corresponding

    Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Berlin Center for Advanced Neuroimaging, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Berlin Center for Advanced Neuroimaging, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

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References 37