학술논문
Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.
Document Type
Academic Journal
Author
Gelpi E; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Klotz S; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Beyerle M; Departments of Neurology, Biomedicine and Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Department of Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.; Wischnewski S; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.; Harter V; Department of Pathology, Klinik Favoriten, 1100 Vienna, Austria.; Kirschner H; Department of Pathology, Klinik Favoriten, 1100 Vienna, Austria.; Stolz K; Department of Forensic Medicine, Medical University of Vienna, 1090 Vienna, Austria.; Reisinger C; Department of Forensic Medicine, Medical University of Vienna, 1090 Vienna, Austria.; Lindeck-Pozza E; Department of Neurology, Klinik Favoriten, 1100 Vienna, Austria.; Zoufaly A; Intensive Care Unit, Klinik Favoriten, 1100 Vienna, Austria.; Faculty of Medicine, Sigmund Freud University, 1020 Vienna, Austria.; Leoni M; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.; Gorkiewicz G; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.; Zacharias M; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.; Haberler C; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Hainfellner J; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Woehrer A; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Hametner S; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Roetzer T; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Voigtländer T; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Ricken G; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Endmayr V; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Haider C; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Ludwig J; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Polt A; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Wilk G; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Schmid S; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Erben I; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Nguyen A; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Lang S; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Simonitsch-Klupp I; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Kornauth C; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Münchner Leukämielabor, 81377 Munich, Germany.; Nackenhorst M; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Kläger J; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Kain R; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Chott A; Institute of Pathology, Klinik Ottakring, 1160 Vienna, Austria.; Wasicky R; Institute of Pathology, Klinik Ottakring, 1160 Vienna, Austria.; Krause R; Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.; Weiss G; Department of Internal Medicine and Pulmonology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Löffler-Rag J; Department of Internal Medicine and Pulmonology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Berger T; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Moser P; Department of Neuropathology, Tirol Kliniken GmbH, 6020 Innsbruck, Austria.; Soleiman A; Department of Neuropathology, Tirol Kliniken GmbH, 6020 Innsbruck, Austria.; Asslaber M; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.; Sedivy R; Department of Pathology, Klinik Favoriten, 1100 Vienna, Austria.; Klupp N; Department of Forensic Medicine, Medical University of Vienna, 1090 Vienna, Austria.; Klimpfinger M; Department of Pathology, Klinik Favoriten, 1100 Vienna, Austria.; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.; Risser D; Department of Forensic Medicine, Medical University of Vienna, 1090 Vienna, Austria.; Budka H; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.; Schirmer L; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Department of Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.; Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.; Pröbstel AK; Departments of Neurology, Biomedicine and Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Department of Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.; Höftberger R; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
Subject
Language
English
Abstract
Background: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms.
Methods: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria.
Results: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%).
Conclusions: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.
Methods: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria.
Results: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%).
Conclusions: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.