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
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.
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.
Inclusion Criteria:
- COVID-19 positive tested
Exclusion Criteria:
- COVID-19 negative tested
- pregnant women
Neurosurgery, University Hospital Basel
Basel, Switzerland
Gregor Hutter, Prof. Dr. med., Principal Investigator
Neurosurgery, University Hospital Basel