Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence

被引：11

作者：

Gelpi, Ellen ^{[1
,2
]}

Klotz, Sigrid ^{[1
,2
]}

Beyerle, Miriam ^{[3
,4
,5
]}

Wischnewski, Sven ^{[6
,7
]}

Harter, Verena ^{[8
]}

Kirschner, Harald ^{[8
]}

Stolz, Katharina ^{[9
]}

Reisinger, Christoph ^{[9
]}

Lindeck-Pozza, Elisabeth ^{[10
]}

Zoufaly, Alexander ^{[11
,12
]}

Leoni, Marlene

Gorkiewicz, Gregor ^{[13
]}

Zacharias, Martin

Haberler, Christine ^{[1
,2
]}

Hainfellner, Johannes ^{[1
,2
]}

Woehrer, Adelheid ^{[1
,2
]}

Hametner, Simon ^{[1
,2
]}

Roetzer, Thomas ^{[1
,2
]}

Voigtlaender, Till ^{[1
,2
]}

Ricken, Gerda ^{[1
,2
]}

Endmayr, Verena ^{[1
,2
]}

Haider, Carmen ^{[1
,2
]}

Ludwig, Judith ^{[1
,2
]}

Polt, Andrea ^{[1
,2
,16
]}

Wilk, Gloria ^{[1
,2
]}

Schmid, Susanne ^{[1
,2
,14
]}

Erben, Irene ^{[1
,2
]}

Nguyen, Anita ^{[1
,2
]}

Lang, Susanna

Simonitsch-Klupp, Ingrid

Kornauth, Christoph ^{[15
]}

Nackenhorst, Maja

Klaeger, Johannes

Kain, Renate

Chott, Andreas

Wasicky, Richard

Krause, Robert ^{[17
]}

Weiss, Guenter ^{[18
]}

Loeffler-Rag, Judith ^{[18
]}

Berger, Thomas ^{[1
,2
,19
]}

Moser, Patrizia ^{[20
]}

Soleiman, Afshin

Asslaber, Martin

Sedivy, Roland ^{[8
]}

Klupp, Nikolaus ^{[9
]}

Klimpfinger, Martin ^{[8
]}

Risser, Daniele ^{[9
]}

Budka, Herbert ^{[1
,2
]}

Schirmer, Lucas ^{[5
,6
,21
]}

Probstel, Anne-Katrin ^{[3
,4
,5
]}

机构：

[1] Med Univ Vienna, Dept Neurol, Div Neuropathol & Neurochem, A-1090 Vienna, Austria

[2] Med Univ Vienna, Comprehens Ctr Clin Neurosci & Mental Hlth, A-1090 Vienna, Austria

[3] Univ Basel, Univ Hosp, Dept Neurol Biomed & Clin Res, CH-4031 Basel, Switzerland

[4] Univ Basel, CH-4031 Basel, Switzerland

[5] Univ Basel, Univ Hosp, Res Ctr Clin Neuroimmunol & Neurosci Basel RC2NB, Dept Clin Res, CH-4031 Basel, Switzerland

[6] Heidelberg Univ, Med Fac Mannheim, Dept Neurol, D-68167 Mannheim, Germany

[7] Mannheim Ctr Translat Neurosci, D-68167 Mannheim, Germany

[8] Klin Favoriten, Dept Pathol, A-1100 Vienna, Austria

[9] Med Univ Vienna, Dept Forens Med, A-1090 Vienna, Austria

[10] Klin Favoriten, Dept Neurol, A-1100 Vienna, Austria

[11] Klin Favoriten, Intens Care Unit, A-1100 Vienna, Austria

[12] Sigmund Freud Univ, Fac Med, A-1020 Vienna, Austria

[13] Med Univ Graz, D&F Inst Pathol, Neuropathol, A-8036 Graz, Austria

[14] Med Univ Vienna, Dept Pathol, A-1090 Vienna, Austria

[15] Munchner Leukamielabor, D-81377 Munich, Germany

[16] Klin Ottakring, Inst Pathol, A-1160 Vienna, Austria

[17] Med Univ Graz, Dept Internal Med, Div Infect Dis, A-8036 Graz, Austria

[18] Med Univ Innsbruck, Dept Internal Med & Pulmonol, A-6020 Innsbruck, Austria

[19] Med Univ Vienna, Dept Neurol, A-1090 Vienna, Austria

[20] Tirol Kliniken GmbH, Dept Neuropathol, A-6020 Innsbruck, Austria

[21] Heidelberg Univ, Interdisciplinary Ctr Neurosci, D-69120 Heidelberg, Germany

来源：

VIRUSES-BASEL | 2023年 / 15卷 / 04期

基金：

欧洲研究理事会; 奥地利科学基金会; 瑞士国家科学基金会;

关键词：

COVID-19; neuropathology; white matter; leukoencephalopathy; SARS-CoV-2; COVID-19;

D O I：

10.3390/v15040908

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：25

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