Multifactorial white matter damage in the acute phase and pre-existing conditions may drive cognitive dysfunction after SARS-CoV-2 infection: neuropathology-based evidence

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 a...

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Hauptverfasser: Gelpi, Ellen (VerfasserIn) , Klotz, Sigrid (VerfasserIn) , Beyerle, Miriam (VerfasserIn) , Wischnewski, Sven (VerfasserIn) , Harter, Verena (VerfasserIn) , Kirschner, Harald (VerfasserIn) , Stolz, Katharina (VerfasserIn) , Reisinger, Christoph (VerfasserIn) , Lindeck-Pozza, Elisabeth (VerfasserIn) , Zoufaly, Alexander (VerfasserIn) , Leoni, Marlene (VerfasserIn) , Gorkiewicz, Gregor (VerfasserIn) , Zacharias, Martin (VerfasserIn) , Haberler, Christine (VerfasserIn) , Hainfellner, Johannes (VerfasserIn) , Woehrer, Adelheid (VerfasserIn) , Hametner, Simon (VerfasserIn) , Roetzer, Thomas (VerfasserIn) , Voigtländer, Till (VerfasserIn) , Ricken, Gerda (VerfasserIn) , Endmayr, Verena (VerfasserIn) , Haider, Carmen (VerfasserIn) , Ludwig, Judith (VerfasserIn) , Polt, Andrea (VerfasserIn) , Wilk, Gloria (VerfasserIn) , Schmid, Susanne (VerfasserIn) , Erben, Irene (VerfasserIn) , Nguyen, Anita (VerfasserIn) , Lang, Susanna (VerfasserIn) , Simonitsch-Klupp, Ingrid (VerfasserIn) , Kornauth, Christoph (VerfasserIn) , Nackenhorst, Maja (VerfasserIn) , Kläger, Johannes (VerfasserIn) , Kain, Renate (VerfasserIn) , Chott, Andreas (VerfasserIn) , Wasicky, Richard (VerfasserIn) , Krause, Robert (VerfasserIn) , Weiss, Günter (VerfasserIn) , Löffler-Rag, Judith (VerfasserIn) , Berger, Thomas (VerfasserIn) , Moser, Patrizia (VerfasserIn) , Soleiman, Afshin (VerfasserIn) , Asslaber, Martin (VerfasserIn) , Sedivy, Roland (VerfasserIn) , Klupp, Nikolaus (VerfasserIn) , Klimpfinger, Martin (VerfasserIn) , Risser, Daniele (VerfasserIn) , Budka, Herbert (VerfasserIn) , Schirmer, Lucas (VerfasserIn) , Pröbstel, Anne-Katrin (VerfasserIn) , Höftberger, Romana (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 31 March 2023
In: Viruses
Year: 2023, Jahrgang: 15, Heft: 4, Pages: 1-25
ISSN:1999-4915
DOI:10.3390/v15040908
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/v15040908
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1999-4915/15/4/908
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Verfasserangaben:Ellen Gelpi, Sigrid Klotz, Miriam Beyerle, Sven Wischnewski, Verena Harter, Harald Kirschner, Katharina Stolz, Christoph Reisinger, Elisabeth Lindeck-Pozza, Alexander Zoufaly, Marlene Leoni, Gregor Gorkiewicz, Martin Zacharias, Christine Haberler, Johannes Hainfellner, Adelheid Woehrer, Simon Hametner, Thomas Roetzer, Till Voigtländer, Gerda Ricken, Verena Endmayr, Carmen Haider, Judith Ludwig, Andrea Polt, Gloria Wilk, Susanne Schmid, Irene Erben, Anita Nguyen, Susanna Lang, Ingrid Simonitsch-Klupp, Christoph Kornauth, Maja Nackenhorst, Johannes Kläger, Renate Kain, Andreas Chott, Richard Wasicky, Robert Krause, Günter Weiss, Judith Löffler-Rag, Thomas Berger, Patrizia Moser, Afshin Soleiman, Martin Asslaber, Roland Sedivy, Nikolaus Klupp, Martin Klimpfinger, Daniele Risser, Herbert Budka, Lucas Schirmer, Anne-Katrin Pröbstel and Romana Höftberger

MARC

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245 1 0 |a Multifactorial white matter damage in the acute phase and pre-existing conditions may drive cognitive dysfunction after SARS-CoV-2 infection  |b neuropathology-based evidence  |c Ellen Gelpi, Sigrid Klotz, Miriam Beyerle, Sven Wischnewski, Verena Harter, Harald Kirschner, Katharina Stolz, Christoph Reisinger, Elisabeth Lindeck-Pozza, Alexander Zoufaly, Marlene Leoni, Gregor Gorkiewicz, Martin Zacharias, Christine Haberler, Johannes Hainfellner, Adelheid Woehrer, Simon Hametner, Thomas Roetzer, Till Voigtländer, Gerda Ricken, Verena Endmayr, Carmen Haider, Judith Ludwig, Andrea Polt, Gloria Wilk, Susanne Schmid, Irene Erben, Anita Nguyen, Susanna Lang, Ingrid Simonitsch-Klupp, Christoph Kornauth, Maja Nackenhorst, Johannes Kläger, Renate Kain, Andreas Chott, Richard Wasicky, Robert Krause, Günter Weiss, Judith Löffler-Rag, Thomas Berger, Patrizia Moser, Afshin Soleiman, Martin Asslaber, Roland Sedivy, Nikolaus Klupp, Martin Klimpfinger, Daniele Risser, Herbert Budka, Lucas Schirmer, Anne-Katrin Pröbstel and Romana Höftberger 
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520 |a 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. 
650 4 |a COVID-19 
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