The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation
Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mil...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Dirk Reinhold [verfasserIn] Vadim Farztdinov [verfasserIn] Yan Yan [verfasserIn] Christian Meisel [verfasserIn] Henrik Sadlowski [verfasserIn] Joachim Kühn [verfasserIn] Frank H. Perschel [verfasserIn] Matthias Endres [verfasserIn] Emrah Düzel [verfasserIn] Stefan Vielhaber [verfasserIn] Karina Guttek [verfasserIn] Alexander Goihl [verfasserIn] Morten Venø [verfasserIn] Bianca Teegen [verfasserIn] Winfried Stöcker [verfasserIn] Paula Stubbemann [verfasserIn] Florian Kurth [verfasserIn] Leif E. Sander [verfasserIn] Markus Ralser [verfasserIn] Carolin Otto [verfasserIn] Simon Streit [verfasserIn] Sven Jarius [verfasserIn] Klemens Ruprecht [verfasserIn] Helena Radbruch [verfasserIn] Jørgen Kjems [verfasserIn] Michael Mülleder [verfasserIn] Frank Heppner [verfasserIn] Peter Körtvelyessy [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Journal of Neuroinflammation - BMC, 2004, 20(2023), 1, Seite 16 |
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| Übergeordnetes Werk: |
volume:20 ; year:2023 ; number:1 ; pages:16 |
| Links: |
|---|
| DOI / URN: |
10.1186/s12974-023-02711-2 |
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| Katalog-ID: |
DOAJ08053578X |
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| 520 | |a Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. | ||
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10.1186/s12974-023-02711-2 doi (DE-627)DOAJ08053578X (DE-599)DOAJ2185b49e6e60455db4212f740b0223ba DE-627 ger DE-627 rakwb eng RC346-429 Dirk Reinhold verfasserin aut The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. COVID-19 Neuroinflammation Proteomics RNA Progranulin Neurology. Diseases of the nervous system Vadim Farztdinov verfasserin aut Yan Yan verfasserin aut Christian Meisel verfasserin aut Henrik Sadlowski verfasserin aut Joachim Kühn verfasserin aut Frank H. Perschel verfasserin aut Matthias Endres verfasserin aut Emrah Düzel verfasserin aut Stefan Vielhaber verfasserin aut Karina Guttek verfasserin aut Alexander Goihl verfasserin aut Morten Venø verfasserin aut Bianca Teegen verfasserin aut Winfried Stöcker verfasserin aut Paula Stubbemann verfasserin aut Florian Kurth verfasserin aut Leif E. Sander verfasserin aut Markus Ralser verfasserin aut Carolin Otto verfasserin aut Simon Streit verfasserin aut Sven Jarius verfasserin aut Klemens Ruprecht verfasserin aut Helena Radbruch verfasserin aut Jørgen Kjems verfasserin aut Michael Mülleder verfasserin aut Frank Heppner verfasserin aut Peter Körtvelyessy verfasserin aut In Journal of Neuroinflammation BMC, 2004 20(2023), 1, Seite 16 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:20 year:2023 number:1 pages:16 https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/article/2185b49e6e60455db4212f740b0223ba kostenfrei https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 16 |
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10.1186/s12974-023-02711-2 doi (DE-627)DOAJ08053578X (DE-599)DOAJ2185b49e6e60455db4212f740b0223ba DE-627 ger DE-627 rakwb eng RC346-429 Dirk Reinhold verfasserin aut The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. COVID-19 Neuroinflammation Proteomics RNA Progranulin Neurology. Diseases of the nervous system Vadim Farztdinov verfasserin aut Yan Yan verfasserin aut Christian Meisel verfasserin aut Henrik Sadlowski verfasserin aut Joachim Kühn verfasserin aut Frank H. Perschel verfasserin aut Matthias Endres verfasserin aut Emrah Düzel verfasserin aut Stefan Vielhaber verfasserin aut Karina Guttek verfasserin aut Alexander Goihl verfasserin aut Morten Venø verfasserin aut Bianca Teegen verfasserin aut Winfried Stöcker verfasserin aut Paula Stubbemann verfasserin aut Florian Kurth verfasserin aut Leif E. Sander verfasserin aut Markus Ralser verfasserin aut Carolin Otto verfasserin aut Simon Streit verfasserin aut Sven Jarius verfasserin aut Klemens Ruprecht verfasserin aut Helena Radbruch verfasserin aut Jørgen Kjems verfasserin aut Michael Mülleder verfasserin aut Frank Heppner verfasserin aut Peter Körtvelyessy verfasserin aut In Journal of Neuroinflammation BMC, 2004 20(2023), 1, Seite 16 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:20 year:2023 number:1 pages:16 https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/article/2185b49e6e60455db4212f740b0223ba kostenfrei https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 16 |
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10.1186/s12974-023-02711-2 doi (DE-627)DOAJ08053578X (DE-599)DOAJ2185b49e6e60455db4212f740b0223ba DE-627 ger DE-627 rakwb eng RC346-429 Dirk Reinhold verfasserin aut The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. COVID-19 Neuroinflammation Proteomics RNA Progranulin Neurology. Diseases of the nervous system Vadim Farztdinov verfasserin aut Yan Yan verfasserin aut Christian Meisel verfasserin aut Henrik Sadlowski verfasserin aut Joachim Kühn verfasserin aut Frank H. Perschel verfasserin aut Matthias Endres verfasserin aut Emrah Düzel verfasserin aut Stefan Vielhaber verfasserin aut Karina Guttek verfasserin aut Alexander Goihl verfasserin aut Morten Venø verfasserin aut Bianca Teegen verfasserin aut Winfried Stöcker verfasserin aut Paula Stubbemann verfasserin aut Florian Kurth verfasserin aut Leif E. Sander verfasserin aut Markus Ralser verfasserin aut Carolin Otto verfasserin aut Simon Streit verfasserin aut Sven Jarius verfasserin aut Klemens Ruprecht verfasserin aut Helena Radbruch verfasserin aut Jørgen Kjems verfasserin aut Michael Mülleder verfasserin aut Frank Heppner verfasserin aut Peter Körtvelyessy verfasserin aut In Journal of Neuroinflammation BMC, 2004 20(2023), 1, Seite 16 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:20 year:2023 number:1 pages:16 https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/article/2185b49e6e60455db4212f740b0223ba kostenfrei https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 16 |
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10.1186/s12974-023-02711-2 doi (DE-627)DOAJ08053578X (DE-599)DOAJ2185b49e6e60455db4212f740b0223ba DE-627 ger DE-627 rakwb eng RC346-429 Dirk Reinhold verfasserin aut The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. COVID-19 Neuroinflammation Proteomics RNA Progranulin Neurology. Diseases of the nervous system Vadim Farztdinov verfasserin aut Yan Yan verfasserin aut Christian Meisel verfasserin aut Henrik Sadlowski verfasserin aut Joachim Kühn verfasserin aut Frank H. Perschel verfasserin aut Matthias Endres verfasserin aut Emrah Düzel verfasserin aut Stefan Vielhaber verfasserin aut Karina Guttek verfasserin aut Alexander Goihl verfasserin aut Morten Venø verfasserin aut Bianca Teegen verfasserin aut Winfried Stöcker verfasserin aut Paula Stubbemann verfasserin aut Florian Kurth verfasserin aut Leif E. Sander verfasserin aut Markus Ralser verfasserin aut Carolin Otto verfasserin aut Simon Streit verfasserin aut Sven Jarius verfasserin aut Klemens Ruprecht verfasserin aut Helena Radbruch verfasserin aut Jørgen Kjems verfasserin aut Michael Mülleder verfasserin aut Frank Heppner verfasserin aut Peter Körtvelyessy verfasserin aut In Journal of Neuroinflammation BMC, 2004 20(2023), 1, Seite 16 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:20 year:2023 number:1 pages:16 https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/article/2185b49e6e60455db4212f740b0223ba kostenfrei https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 16 |
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10.1186/s12974-023-02711-2 doi (DE-627)DOAJ08053578X (DE-599)DOAJ2185b49e6e60455db4212f740b0223ba DE-627 ger DE-627 rakwb eng RC346-429 Dirk Reinhold verfasserin aut The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. COVID-19 Neuroinflammation Proteomics RNA Progranulin Neurology. Diseases of the nervous system Vadim Farztdinov verfasserin aut Yan Yan verfasserin aut Christian Meisel verfasserin aut Henrik Sadlowski verfasserin aut Joachim Kühn verfasserin aut Frank H. Perschel verfasserin aut Matthias Endres verfasserin aut Emrah Düzel verfasserin aut Stefan Vielhaber verfasserin aut Karina Guttek verfasserin aut Alexander Goihl verfasserin aut Morten Venø verfasserin aut Bianca Teegen verfasserin aut Winfried Stöcker verfasserin aut Paula Stubbemann verfasserin aut Florian Kurth verfasserin aut Leif E. Sander verfasserin aut Markus Ralser verfasserin aut Carolin Otto verfasserin aut Simon Streit verfasserin aut Sven Jarius verfasserin aut Klemens Ruprecht verfasserin aut Helena Radbruch verfasserin aut Jørgen Kjems verfasserin aut Michael Mülleder verfasserin aut Frank Heppner verfasserin aut Peter Körtvelyessy verfasserin aut In Journal of Neuroinflammation BMC, 2004 20(2023), 1, Seite 16 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:20 year:2023 number:1 pages:16 https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/article/2185b49e6e60455db4212f740b0223ba kostenfrei https://doi.org/10.1186/s12974-023-02711-2 kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 16 |
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Dirk Reinhold @@aut@@ Vadim Farztdinov @@aut@@ Yan Yan @@aut@@ Christian Meisel @@aut@@ Henrik Sadlowski @@aut@@ Joachim Kühn @@aut@@ Frank H. Perschel @@aut@@ Matthias Endres @@aut@@ Emrah Düzel @@aut@@ Stefan Vielhaber @@aut@@ Karina Guttek @@aut@@ Alexander Goihl @@aut@@ Morten Venø @@aut@@ Bianca Teegen @@aut@@ Winfried Stöcker @@aut@@ Paula Stubbemann @@aut@@ Florian Kurth @@aut@@ Leif E. Sander @@aut@@ Markus Ralser @@aut@@ Carolin Otto @@aut@@ Simon Streit @@aut@@ Sven Jarius @@aut@@ Klemens Ruprecht @@aut@@ Helena Radbruch @@aut@@ Jørgen Kjems @@aut@@ Michael Mülleder @@aut@@ Frank Heppner @@aut@@ Peter Körtvelyessy @@aut@@ |
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The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation |
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Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. |
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Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. |
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Abstract Patients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation. |
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