Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas
IntroductionThis study aimed to investigate microglial and macrophage activation in 17 patients who died in the context of a COVID-19 infection in 2020 and 2021.MethodsThrough immunohistochemical analysis, the lysosomal marker CD68 was used to detect diffuse parenchymal microglial activity, pronounc...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-07-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1229641/full |
| _version_ | 1797780758183542784 |
|---|---|
| author | Julian A. Stein Manuel Kaes Sigrun Smola Sigrun Smola Walter J. Schulz-Schaeffer |
| author_facet | Julian A. Stein Manuel Kaes Sigrun Smola Sigrun Smola Walter J. Schulz-Schaeffer |
| author_sort | Julian A. Stein |
| collection | DOAJ |
| description | IntroductionThis study aimed to investigate microglial and macrophage activation in 17 patients who died in the context of a COVID-19 infection in 2020 and 2021.MethodsThrough immunohistochemical analysis, the lysosomal marker CD68 was used to detect diffuse parenchymal microglial activity, pronounced perivascular macrophage activation and macrophage clusters. COVID-19 patients were compared to control patients and grouped regarding clinical aspects. Detection of viral proteins was attempted in different regions through multiple commercially available antibodies.ResultsMicroglial and macrophage activation was most pronounced in the white matter with emphasis in brain stem and cerebellar areas. Analysis of lesion patterns yielded no correlation between disease severity and neuropathological changes. Occurrence of macrophage clusters could not be associated with a severe course of disease or preconditions but represent a more advanced stage of microglial and macrophage activation. Severe neuropathological changes in COVID-19 were comparable to severe Influenza. Hypoxic damage was not a confounder to the described neuropathology. The macrophage/microglia reaction was less pronounced in post COVID-19 patients, but detectable i.e. in the brain stem. Commercially available antibodies for detection of SARS-CoV-2 virus material in immunohistochemistry yielded no specific signal over controls.ConclusionThe presented microglial and macrophage activation might be an explanation for the long COVID syndrome. |
| first_indexed | 2024-03-12T23:48:23Z |
| format | Article |
| id | doaj.art-637438bc94f246bea89efb90fe4be06e |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-12T23:48:23Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-637438bc94f246bea89efb90fe4be06e2023-07-14T02:12:27ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-07-011410.3389/fneur.2023.12296411229641Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areasJulian A. Stein0Manuel Kaes1Sigrun Smola2Sigrun Smola3Walter J. Schulz-Schaeffer4Institute of Neuropathology, Medical Faculty of the Saarland University, Homburg, GermanyInstitute of Neuropathology, Medical Faculty of the Saarland University, Homburg, GermanyInstitute of Virology, Saarland University Medical Center, Homburg, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarbrücken, GermanyInstitute of Neuropathology, Medical Faculty of the Saarland University, Homburg, GermanyIntroductionThis study aimed to investigate microglial and macrophage activation in 17 patients who died in the context of a COVID-19 infection in 2020 and 2021.MethodsThrough immunohistochemical analysis, the lysosomal marker CD68 was used to detect diffuse parenchymal microglial activity, pronounced perivascular macrophage activation and macrophage clusters. COVID-19 patients were compared to control patients and grouped regarding clinical aspects. Detection of viral proteins was attempted in different regions through multiple commercially available antibodies.ResultsMicroglial and macrophage activation was most pronounced in the white matter with emphasis in brain stem and cerebellar areas. Analysis of lesion patterns yielded no correlation between disease severity and neuropathological changes. Occurrence of macrophage clusters could not be associated with a severe course of disease or preconditions but represent a more advanced stage of microglial and macrophage activation. Severe neuropathological changes in COVID-19 were comparable to severe Influenza. Hypoxic damage was not a confounder to the described neuropathology. The macrophage/microglia reaction was less pronounced in post COVID-19 patients, but detectable i.e. in the brain stem. Commercially available antibodies for detection of SARS-CoV-2 virus material in immunohistochemistry yielded no specific signal over controls.ConclusionThe presented microglial and macrophage activation might be an explanation for the long COVID syndrome.https://www.frontiersin.org/articles/10.3389/fneur.2023.1229641/fullCOVID-19neuropathologymacrophageCD68immunohistochemistryCNS infection |
| spellingShingle | Julian A. Stein Manuel Kaes Sigrun Smola Sigrun Smola Walter J. Schulz-Schaeffer Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas Frontiers in Neurology COVID-19 neuropathology macrophage CD68 immunohistochemistry CNS infection |
| title | Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas |
| title_full | Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas |
| title_fullStr | Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas |
| title_full_unstemmed | Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas |
| title_short | Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas |
| title_sort | neuropathology in covid 19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas |
| topic | COVID-19 neuropathology macrophage CD68 immunohistochemistry CNS infection |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1229641/full |
| work_keys_str_mv | AT julianastein neuropathologyincovid19autopsiesisdefinedbymicroglialactivationandlesionsofthewhitematterwithemphasisincerebellarandbrainstemareas AT manuelkaes neuropathologyincovid19autopsiesisdefinedbymicroglialactivationandlesionsofthewhitematterwithemphasisincerebellarandbrainstemareas AT sigrunsmola neuropathologyincovid19autopsiesisdefinedbymicroglialactivationandlesionsofthewhitematterwithemphasisincerebellarandbrainstemareas AT sigrunsmola neuropathologyincovid19autopsiesisdefinedbymicroglialactivationandlesionsofthewhitematterwithemphasisincerebellarandbrainstemareas AT walterjschulzschaeffer neuropathologyincovid19autopsiesisdefinedbymicroglialactivationandlesionsofthewhitematterwithemphasisincerebellarandbrainstemareas |