Clinical trial NCT04472013: Systematic Assessment of SARS-CoV-2 Neurotropic Capacity in Modestly and Critically Ill Patients, and Patients Who Died From COVID-19
Official title: Systematic Assessment of SARS-CoV-2 Neurotropic Capacity in Modestly and Critically Ill Patients, and Patients Who Died From COVID-19
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19 Disease
Keywords: SARS-CoV-2
neurotropism of SARS-CoV-2
microglia
CODEX (high dimensional microscopy) analysis
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Botnar Research Centre for Child Health
First posted: 2020-07-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: Inclusion Criteria:

* COVID-19 positive tested

Exclusion Criteria:

* COVID-19 negative tested
* pregnant women

Primary outcomes:
measure: MRI imaging data
timeFrame: Project duration for each patient takes 1 hour for the MRI at baseline
measure: Proteomic analysis
timeFrame: 10 minutes for blood draw at baseline
measure: Peripheral blood leukocyte Cytof Mass Cytometry Analysis for cell population frequency
timeFrame: 10 minutes for blood draw at baseline
measure: CODEX (high dimensional microscopy) workflow analysis of defined regions on brain autopsy specimens
timeFrame: at baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Neurosurgery, University Hospital Basel
Study officials:
affiliation: Neurosurgery, University Hospital Basel
name: Gregor Hutter, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.