Systematic Assessment of SARS-CoV-2 Neurotropic Capacity in Modestly and Critically Ill Patients, and Patients Who Died From COVID-19
NCT04472013 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 40
Last updated 2025-01-22
Summary
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
Conditions
- COVID-19 Disease
Interventions
- OTHER
-
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.
- OTHER
-
Data collection from blood draw
Plasma samples will be acquired for plasma cytokine proteomics using CyTOF (mass cytometry analysis) technology.
- 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.
- 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.
Sponsors & Collaborators
-
Botnar Research Centre for Child Health
collaborator UNKNOWN -
University Hospital, Basel, Switzerland
lead OTHER
Principal Investigators
-
Gregor Hutter, Prof. Dr. med. · Neurosurgery, University Hospital Basel
Eligibility
- Min Age
- 18 Years
- Sex
- ALL
- Healthy Volunteers
- No
Timeline & Regulatory
- Start
- 2020-08-12
- Primary Completion
- 2022-11-09
- Completion
- 2022-11-09
Countries
- Switzerland
Study Locations
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