Systematic Assessment of SARS-CoV-2 Neurotropic Capacity in Modestly and Critically Ill Patients, and Patients Who Died From COVID-19

NCT ID: NCT04472013

Last Updated: 2025-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-12

Study Completion Date

2022-11-09

Brief Summary

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This study is to analyze the microglia reaction or direct neurotropic effects of CNS COVID-19 in pathogenesis and brain stem dysfunction in critically ill patients. A microglia-focused, brain-specific 50+ marker CODEX panel is used to assess the neuroinflammatory microenvironment in specific brain regions of deceased COVID-19 patients. The peripheral (cerebrospinal fluid and peripheral blood) cytokine response to SARS-CoV-2 is investigated in regard to CNS affection and consecutive blood brain barrier disruption leading to braininherent neuroinflammatory reactions

Detailed Description

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This study is to analyze the microglia reaction or direct neurotropic effects of CNS COVID-19 in pathogenesis and brain stem dysfunction in critically ill patients. A microglia-focused, brain-specific 50+ marker CODEX panel is used to assess the neuroinflammatory microenvironment in specific brain regions of deceased COVID-19 patients. The peripheral (cerebrospinal fluid and peripheral blood) cytokine response to SARS-CoV-2 is investigated in regard to CNS affection and consecutive blood brain barrier disruption leading to braininherent neuroinflammatory reactions. Primary endpoints of this project are the multidimensional integration of the analysis from the procedures described above and assessment of the correlation between the gained clinical data (MRI, mental/neurological state), the body fluid proteomic and mass-cytometric analysis (CSF and Plasma proteomics, peripheral blood mass cytometry) and the CODEX analysis of defined brain regions on autopsy specimens.

Non-critically ill COVID-19 patients and critically ill COVID-19 patients needing mechanical ventilation at the ICU are included. Autopsy specimens from medulla oblongata, cortex, cerebellum and olfactory bulb are investigated, including only tissue samples, which have been submitted to the Institute of Pathology, University Hospital Basel.

Conditions

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COVID-19 Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Data collection from lumbar puncture

Cerebro spinal fluid (CSF) will be acquired by lumbar puncture and sent for routine analysis including CSF chemistry, cytology and microbiology. Targeted CSF proteomics using OLINK Proximity Extension Assay (PEA) technology to assess a potential CNS-contribution of the disease will be performed.

Intervention Type OTHER

Data collection from blood draw

Plasma samples will be acquired for plasma cytokine proteomics using CyTOF (mass cytometry analysis) technology.

Intervention Type OTHER

CNS magnetic resonance imaging (MRI) imaging

3Tesla magnetic resonance imaging (MRI) will be performed to document early/manifest encephalitic changes in COVID-19 patients.

Intervention Type OTHER

Microscopy of defined brain regions on autopsy specimens

High dimensional, microglia-centric CODEX fluorescent microscopy of defined brain regions on autopsy specimens will be acquired from medulla oblongata, cortex, cerebellum, and olfactory bulb. A brain-specific CODEX panel for the assessment of the immune microenvironment was implemented, with inclusion of a wide array of myeloid/microglia markers, T-cell markers, and a few neuronal markers. All the antibodies have been validated and tested in formalin-fixed tissues of different zones of glioblastoma tumors including invading tumor periphery. The Panel will be modified to include the viral entry receptors, CD147, ACE2 and TMPRSS2. Presence of SARS-CoV-2 virus particles will be assessed by qPCR, andMultiplexed Ion Beam Imaging (MIBI) technology will be used to visualize tropism of virus to specific cellular brain compartments.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* COVID-19 positive tested

Exclusion Criteria

* COVID-19 negative tested
* pregnant women
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Botnar Research Centre for Child Health

UNKNOWN

Sponsor Role collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gregor Hutter, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Neurosurgery, University Hospital Basel

Locations

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Neurosurgery, University Hospital Basel

Basel, , Switzerland

Site Status

Countries

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Switzerland

References

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Etter MM, Martins TA, Kulsvehagen L, Possnecker E, Duchemin W, Hogan S, Sanabria-Diaz G, Muller J, Chiappini A, Rychen J, Eberhard N, Guzman R, Mariani L, Melie-Garcia L, Keller E, Jelcic I, Pargger H, Siegemund M, Kuhle J, Oechtering J, Eich C, Tzankov A, Matter MS, Uzun S, Yaldizli O, Lieb JM, Psychogios MN, Leuzinger K, Hirsch HH, Granziera C, Probstel AK, Hutter G. Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study. Nat Commun. 2022 Nov 9;13(1):6777. doi: 10.1038/s41467-022-34068-0.

Reference Type RESULT
PMID: 36351919 (View on PubMed)

Related Links

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http://doi.org/10.1038/s41467-022-34068-0

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Other Identifiers

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2020-01503; ch20Hutter

Identifier Type: -

Identifier Source: org_study_id

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