Neurotropism and Neuroinflammation in COVID-19 Patients With Delirium.

Completed

• Conditions: Post-traumatic Stress Disorder; Covid19; Delirium
• Interventions: Biological: serology testing profiles description; Biological: immune response characterization; Other: in vivo brain PET-TSPO acquisitions; Other: brain MRI assessment; Behavioral: neurocognitive assessment

• Registration Number: NCT04785157
• Lead Sponsor: University Hospital, Toulouse

Brief Summary

Emerging evidence indicates that SARS-CoV-2, the etiologic agent of COVID-19, can cause neurological, neuropsychological and psychiatric complications. Given the global dimensions of the current pandemic, there is to consider the possible large-scale neurocognitive impact of COVID-19. Therefore, there is an urgent need for longitudinal studies to determine the acute and chronic effects that COVID-19 may have on the Central Nervous System. These putative effects include the possibility that the CNS serves as a reservoir for the virus, and that COVID-19 triggers CNS deleterious inflammatory cascades and neurodegenerative process. The public implications of these effects are very important in the long term.

Detailed Description

The BRAINSTORM project aims at creating a proof-of-concept dataset from severe COVID-19 patients with delirium. For the first time, this longitudinal study will rely on repeated and concomitant: i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF), ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF), iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia), iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity), v) multi-domains neurocognitive assessment. This dataset will be made FAIR to allow open data use and to prepare future studies.

Study Timeline

• Study First Submitted: 2021-03-02
• Study First Submitted QC: 2021-03-04
• Study First Posted: 2021-03-05
• Study Start: 2021-06-01
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-22
• Last Update Posted: 2023-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Adult patients (male or female > or = 18 years)
• COVID-19 (positive respiratory track PCR test < 30 days)
• Delirium (CAM-ICU criteria)
• informed and written consent to participate in the study by patient's surrogate.

Exclusion Criteria

• medical decision of withdrawal of life sustaining treatments previous to patients recruitment
• former neurological or psychiatric disability
• MRI or PET scan contraindication
• pregnancy
• hemodynamic or respiratory failure precluding patient's transport / MRI or PET scanning

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
severe COVID-19 patients with delirium	immune response characterization	i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF) ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF) iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia) iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity) v) multi-domains neurocognitive assessment.
severe COVID-19 patients with delirium	brain MRI assessment	i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF) ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF) iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia) iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity) v) multi-domains neurocognitive assessment.
severe COVID-19 patients with delirium	serology testing profiles description	i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF) ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF) iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia) iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity) v) multi-domains neurocognitive assessment.
severe COVID-19 patients with delirium	in vivo brain PET-TSPO acquisitions	i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF) ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF) iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia) iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity) v) multi-domains neurocognitive assessment.
severe COVID-19 patients with delirium	neurocognitive assessment	i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF) ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF) iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia) iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity) v) multi-domains neurocognitive assessment.

Primary Outcome Measures

Name	Time	Method
PET imaging examination	Month 3	Intensity and topography of \[18F\]DPA-714-labeled microglial activation in vivo in PET imaging examination

Secondary Outcome Measures

Name	Time	Method
multimodal MRI 3 months after the acute delirium phase	month 3	Imaging criteria: Structural-functional disconnects at the whole brain level (multimodal MRI)
SARS-CoV-2 quasispecies detection in acute delirium phase in cerebrospinal fluid specimen	Day 0	SARS-CoV-2 quasispecies detection in cerebrospinal fluid specimen
SARS-CoV-2 quasispecies detection in acute delirium phase in blood specimen	Day 0	SARS-CoV-2 quasispecies detection in blood specimen
multimodal MRI in acute delirium phase	Day 0	Imaging criteria: Structural-functional disconnects at the whole brain level (multimodal MRI)
SARS-CoV-2 quasispecies detection 3 month after the acute delirium phase in cerebrospinal fluid specimen	Month 3	SARS-CoV-2 quasispecies detection in cerebrospinal fluid specimen
SARS-CoV-2 quasispecies detection 3 month after the acute delirium phase in blood specimen	Month 3	SARS-CoV-2 quasispecies detection in blood specimen

Trial Locations

Locations (2)

University Hospital of Toulouse; 🇫🇷 Toulouse, France

CHRU Tours; 🇫🇷 Tours, France