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

Autor:	Heine J; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Schwichtenberg K; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Hartung TJ; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Rekers S; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany., Chien C; 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., Boesl F; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Rust R; 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., Hohenfeld C; 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., Bungenberg J; 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., Costa AS; 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., Scheibenbogen C; Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Bellmann-Strobl J; 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., Paul F; 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., Franke C; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Reetz K; 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., Finke C; 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.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2023 Apr; Vol. 58, pp. 101874. Date of Electronic Publication: 2023 Feb 27.
DOI:	10.1016/j.eclinm.2023.101874
Abstrakt:	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). Competing Interests: Dr. Chien reports personal fees from Bayer, grants from Novartis, outside the submitted work. Dr. Bellmann-Strobl reports personal fees from Bayer Healthcare, personal fees from sanofi-aventis/Genzyme, personal fees from Roche, outside the submitted work. Dr. Paul reports personal fees and non-financial support from SanofiGenzyme, personal fees, non-financial support and other from BiogenIdec, personal fees and non-financial support from MedImmune, personal fees and non-financial support from Shire, personal fees and non-financial support from Alexion, grants, personal fees and non-financial support from Bayer, grants and personal fees from Novartis, grants and personal fees from Teva, grants and personal fees from Merck Serono, personal fees from Actelion, personal fees from Chugai, personal fees from Roche, personal fees from Celgene, grants from Sanofi-Aventis/Genzyme, grants from Alexion, grants from German Research Council (DFG Exc 257), grants from Werth Stiftung of the City of Cologne, grants from German Ministry of Education and Research (BMBF Competence Network Multiple Sclerosis), grants from Arthur Arnstein Stiftung Berlin, grants from EU FP7 Framework Program (combims.eu), grants from Guthy Jackson Charitable Foundation, grants from National Multiple Sclerosis Society of the USA, outside the submitted work. All other authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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