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SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature

INTRODUCTION: COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients...

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Autores principales: Lebrun, Laetitia, Absil, Lara, Remmelink, Myriam, De Mendonça, Ricardo, D’Haene, Nicky, Gaspard, Nicolas, Rusu, Stefan, Racu, Marie-Lucie, Collin, Amandine, Allard, Justine, Zindy, Egor, Schiavo, Andrea Alex, De Clercq, Sarah, De Witte, Olivier, Decaestecker, Christine, Lopes, Maria-Beatriz, Salmon, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170054/
https://www.ncbi.nlm.nih.gov/pubmed/37165453
http://dx.doi.org/10.1186/s40478-023-01566-1
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author Lebrun, Laetitia
Absil, Lara
Remmelink, Myriam
De Mendonça, Ricardo
D’Haene, Nicky
Gaspard, Nicolas
Rusu, Stefan
Racu, Marie-Lucie
Collin, Amandine
Allard, Justine
Zindy, Egor
Schiavo, Andrea Alex
De Clercq, Sarah
De Witte, Olivier
Decaestecker, Christine
Lopes, Maria-Beatriz
Salmon, Isabelle
author_facet Lebrun, Laetitia
Absil, Lara
Remmelink, Myriam
De Mendonça, Ricardo
D’Haene, Nicky
Gaspard, Nicolas
Rusu, Stefan
Racu, Marie-Lucie
Collin, Amandine
Allard, Justine
Zindy, Egor
Schiavo, Andrea Alex
De Clercq, Sarah
De Witte, Olivier
Decaestecker, Christine
Lopes, Maria-Beatriz
Salmon, Isabelle
author_sort Lebrun, Laetitia
collection PubMed
description INTRODUCTION: COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. MATERIAL AND METHODS: We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. RESULTS: In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. CONCLUSION: This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01566-1.
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spelling pubmed-101700542023-05-11 SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature Lebrun, Laetitia Absil, Lara Remmelink, Myriam De Mendonça, Ricardo D’Haene, Nicky Gaspard, Nicolas Rusu, Stefan Racu, Marie-Lucie Collin, Amandine Allard, Justine Zindy, Egor Schiavo, Andrea Alex De Clercq, Sarah De Witte, Olivier Decaestecker, Christine Lopes, Maria-Beatriz Salmon, Isabelle Acta Neuropathol Commun Research INTRODUCTION: COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. MATERIAL AND METHODS: We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. RESULTS: In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. CONCLUSION: This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01566-1. BioMed Central 2023-05-10 /pmc/articles/PMC10170054/ /pubmed/37165453 http://dx.doi.org/10.1186/s40478-023-01566-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lebrun, Laetitia
Absil, Lara
Remmelink, Myriam
De Mendonça, Ricardo
D’Haene, Nicky
Gaspard, Nicolas
Rusu, Stefan
Racu, Marie-Lucie
Collin, Amandine
Allard, Justine
Zindy, Egor
Schiavo, Andrea Alex
De Clercq, Sarah
De Witte, Olivier
Decaestecker, Christine
Lopes, Maria-Beatriz
Salmon, Isabelle
SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
title SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
title_full SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
title_fullStr SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
title_full_unstemmed SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
title_short SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
title_sort sars-cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170054/
https://www.ncbi.nlm.nih.gov/pubmed/37165453
http://dx.doi.org/10.1186/s40478-023-01566-1
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