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Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.
Gelpi, Ellen; Klotz, Sigrid; Beyerle, Miriam; Wischnewski, Sven; Harter, Verena; Kirschner, Harald; Stolz, Katharina; Reisinger, Christoph; Lindeck-Pozza, Elisabeth; Zoufaly, Alexander; Leoni, Marlene; Gorkiewicz, Gregor; Zacharias, Martin; Haberler, Christine; Hainfellner, Johannes; Woehrer, Adelheid; Hametner, Simon; Roetzer, Thomas; Voigtländer, Till; Ricken, Gerda; Endmayr, Verena; Haider, Carmen; Ludwig, Judith; Polt, Andrea; Wilk, Gloria; Schmid, Susanne; Erben, Irene; Nguyen, Anita; Lang, Susanna; Simonitsch-Klupp, Ingrid; Kornauth, Christoph; Nackenhorst, Maja; Kläger, Johannes; Kain, Renate; Chott, Andreas; Wasicky, Richard; Krause, Robert; Weiss, Günter; Löffler-Rag, Judith; Berger, Thomas; Moser, Patrizia; Soleiman, Afshin; Asslaber, Martin; Sedivy, Roland; Klupp, Nikolaus; Klimpfinger, Martin; Risser, Daniele; Budka, Herbert; Schirmer, Lucas; Pröbstel, Anne-Katrin.
  • Gelpi E; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Klotz S; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Beyerle M; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Wischnewski S; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Harter V; Departments of Neurology, Biomedicine and Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.
  • Kirschner H; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Department of Clinical Research, University Hospital and University of Basel, 4031 Basel, Switzerland.
  • Stolz K; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
  • Reisinger C; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
  • Lindeck-Pozza E; Department of Pathology, Klinik Favoriten, 1100 Vienna, Austria.
  • Zoufaly A; Department of Pathology, Klinik Favoriten, 1100 Vienna, Austria.
  • Leoni M; Department of Forensic Medicine, Medical University of Vienna, 1090 Vienna, Austria.
  • Gorkiewicz G; Department of Forensic Medicine, Medical University of Vienna, 1090 Vienna, Austria.
  • Zacharias M; Department of Neurology, Klinik Favoriten, 1100 Vienna, Austria.
  • Haberler C; Intensive Care Unit, Klinik Favoriten, 1100 Vienna, Austria.
  • Hainfellner J; Faculty of Medicine, Sigmund Freud University, 1020 Vienna, Austria.
  • Woehrer A; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.
  • Hametner S; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.
  • Roetzer T; D&F Institute of Pathology, Neuropathology, Medical University Graz, 8036 Graz, Austria.
  • Voigtländer T; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Ricken G; 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.
  • Haider C; 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.
  • Polt A; 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.
  • Schmid S; 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.
  • Nguyen A; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Lang S; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Simonitsch-Klupp I; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Kornauth C; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Nackenhorst M; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Kläger J; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Kain R; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Chott A; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Wasicky R; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Krause R; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Weiss G; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Löffler-Rag J; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Berger T; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Moser P; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Soleiman A; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Asslaber M; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Sedivy R; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Klupp N; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Klimpfinger M; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Risser D; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
  • Budka H; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, 1090 Vienna, Austria.
  • Schirmer L; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.
  • Pröbstel AK; Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.
Viruses ; 15(4)2023 03 31.
Article in English | MEDLINE | ID: covidwho-2295438
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cognitive Dysfunction / White Matter / COVID-19 / Nervous System Diseases / Neuritis Type of study: Prognostic study Topics: Long Covid Limits: Aged / Humans Language: English Year: 2023 Document Type: Article Affiliation country: V15040908

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cognitive Dysfunction / White Matter / COVID-19 / Nervous System Diseases / Neuritis Type of study: Prognostic study Topics: Long Covid Limits: Aged / Humans Language: English Year: 2023 Document Type: Article Affiliation country: V15040908