Systematic Assessment of SARS-CoV-2 Neurotropic Capacity in Modestly and Critically Ill Patients, and Patients Who Died From COVID-19
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- COVID-19 Disease
- Sponsor
- University Hospital, Basel, Switzerland
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Proteomic analysis
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •COVID-19 positive tested
Exclusion Criteria
- •COVID-19 negative tested
- •pregnant women
Outcomes
Primary Outcomes
Proteomic analysis
Time Frame: 10 minutes for blood draw at baseline
Description of proteomic biomarkers (CSF and Plasma) in comparison with control reference sample.
CODEX (high dimensional microscopy) workflow analysis of defined regions on brain autopsy specimens
Time Frame: at baseline
In situ distribution assessment of marker expression (CD147 protein, ACE2 protein, Transmembrane protease serine subtype 2 (TMPRSS2))
Peripheral blood leukocyte Cytof Mass Cytometry Analysis for cell population frequency
Time Frame: 10 minutes for blood draw at baseline
Mass cytometry will be performed form peripheral blood mononuclear cells to count cell population frequency.
MRI imaging data
Time Frame: Project duration for each patient takes 1 hour for the MRI at baseline
Comparison of lesions from patients that are neurologically affected to non-affected individuals in terms of CNS involvement to describe encephalitic changes due to COVID-19 infection.