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

Completed

• Conditions: COVID-19 Disease

• Registration Number: NCT04472013
• Lead Sponsor: 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

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.

Study Timeline

• Study First Submitted: 2020-07-14
• Study First Submitted QC: 2020-07-14
• Study First Posted: 2020-07-15
• Study Start: 2020-08-12
• Status Verified: 2022-11
• Primary Completion: 2022-11-09
• Study Completion: 2022-11-09
• Last Update Submitted: 2025-01-17
• Last Update Posted: 2025-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• COVID-19 positive tested

Exclusion Criteria

• COVID-19 negative tested
• pregnant women

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proteomic analysis	10 minutes for blood draw at baseline	Description of proteomic biomarkers (CSF and Plasma) in comparison with control reference sample.
Peripheral blood leukocyte Cytof Mass Cytometry Analysis for cell population frequency	10 minutes for blood draw at baseline	Mass cytometry will be performed form peripheral blood mononuclear cells to count cell population frequency.
CODEX (high dimensional microscopy) workflow analysis of defined regions on brain autopsy specimens	at baseline	In situ distribution assessment of marker expression (CD147 protein, ACE2 protein, Transmembrane protease serine subtype 2 (TMPRSS2))
MRI imaging data	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.

Trial Locations

Locations (1)

Neurosurgery, University Hospital Basel; 🇨🇭 Basel, Switzerland