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

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ClinicalTrials.gov Identifier: NCT04472013
Recruitment Status : Recruiting
First Posted : July 15, 2020
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Botnar Research Centre for Child Health
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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

Condition or disease Intervention/treatment
COVID-19 Disease Other: Data collection from lumbar puncture Other: Data collection from blood draw Other: CNS magnetic resonance imaging (MRI) imaging Other: Microscopy of defined brain regions on autopsy specimens

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.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Systematic Assessment of SARS-CoV-2 Neurotropic Capacity in Modestly and Critically Ill Patients, and Patients Who Died From COVID-19
Actual Study Start Date : August 12, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Intervention Details:
  • 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.


Primary Outcome Measures :
  1. 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.

  2. Proteomic analysis [ Time Frame: 10 minutes for blood draw at baseline ]
    Description of proteomic biomarkers (CSF and Plasma) in comparison with control reference sample.

  3. 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.

  4. 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))


Biospecimen Retention:   Samples Without DNA
Biological material is appropriately stored in a restricted area only accessible to authorized personnel. The acquired fluids of lumbar puncture, blood withdrawal and autopsy (in case of death) are going to be frozen at -80° C and stored at Department of Biomedicine, University Hospital of Basel. Biological material in this project is not identified by participant name but by a unique participant number.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
20 non-critically ill COVID-19 patients from the inpatient ward, and 20 critically ill COVID-19 patients needing mechanical ventilation at the ICU. Recruitment takes places at University Hospital of Basel and the Kantonsspital Baselland Liestal.
Criteria

Inclusion Criteria:

  • COVID-19 positive tested

Exclusion Criteria:

  • COVID-19 negative tested
  • pregnant women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04472013


Contacts
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Contact: Gregor Hutter, Prof. Dr. med. +41 61 328 50 68 Gregor.hutter@usb.ch

Locations
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Switzerland
Neurosurgery, University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Gregor Hutter, Prof. Dr. med.    +41 61 328 50 68    gregor.hutter@usb.ch   
Kantonsspital Baselland Liestal Recruiting
Liestal, Switzerland, 4410
Contact: David Winkler, PD Dr. med.    +41 61 925 37 00    david.winkler@ksbl.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Botnar Research Centre for Child Health
Investigators
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Principal Investigator: Gregor Hutter, Prof. Dr. med. Neurosurgery, University Hospital Basel
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT04472013    
Other Study ID Numbers: 2020-01503; ch20Hutter
First Posted: July 15, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Basel, Switzerland:
SARS-CoV-2
neurotropism of SARS-CoV-2
microglia
CODEX (high dimensional microscopy) analysis
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes