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

NCT04472013 | Completed

• 1 other identifier: 2020-01503; ch20Hutter
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

COVID-19 Disease

Keywords

SARS-CoV-2; neurotropism of SARS-CoV-2; microglia; CODEX (high dimensional microscopy) analysis

Outcome Measures

Primary Outcomes (4)

• MRI imaging data

  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.

  Project duration for each patient takes 1 hour for the MRI at baseline

• Proteomic analysis

  Description of proteomic biomarkers (CSF and Plasma) in comparison with control reference sample.

  10 minutes for blood draw at baseline

• Peripheral blood leukocyte Cytof Mass Cytometry Analysis for cell population frequency

  Mass cytometry will be performed form peripheral blood mononuclear cells to count cell population frequency.

  10 minutes for blood draw at baseline

• CODEX (high dimensional microscopy) workflow analysis of defined regions on brain autopsy specimens

  In situ distribution assessment of marker expression (CD147 protein, ACE2 protein, Transmembrane protease serine subtype 2 (TMPRSS2))

  at baseline

Interventions

Data collection from lumbar puncture OTHER

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.

Data collection from blood draw OTHER

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

CNS magnetic resonance imaging (MRI) imaging OTHER

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

Microscopy of defined brain regions on autopsy specimens OTHER

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• COVID-19 positive tested

You may not qualify if:

• COVID-19 negative tested
• pregnant women

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Botnar Research Centre for Child Health: collaborator

Study Sites (1)

Neurosurgery, University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 36351919 RESULT

Related Links

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

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.

MeSH Terms

Interventions

Magnetic Resonance Spectroscopy; X-Rays

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Gregor Hutter, Prof. Dr. med.

  Neurosurgery, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 15, 2020
• Study Start: August 12, 2020
• Primary Completion: November 9, 2022
• Study Completion: November 9, 2022
• Last Updated: January 22, 2025

Record last verified: 2022-11

Locations

CH (1)