Neurotropism and Neuroinflammation in COVID-19 Patients With Delirium. (BRAINSTORM)

SARS-CoV-2 Neurotropism, micRoglial ActivatioN and Cytokine dySregulaTiOn in COVID-19 Patients With Delirium

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.

Study Overview

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

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 Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

• Study Contact: Name: Stein SILVA, MD, PhD; Phone Number: +33 05 61 77 97 28; Email: silva.s@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France
    • University Hospital of Toulouse
  • Tours, France
    • CHRU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

patients from hospital

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

severe COVID-19 patients with delirium; 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.

Biological: serology testing profiles description; SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF); Other Names: biomarkers; Biological: immune response characterization; systemic and central immune response characterization , associated to the assessment of CNS damage biomarkers (peripheral blood and CSF); Other: in vivo brain PET-TSPO acquisitions; in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia); Other: brain MRI assessment; structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity); Behavioral: neurocognitive assessment; multi-domains neurocognitive assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET imaging examination	Intensity and topography of [18F]DPA-714-labeled microglial activation in vivo in PET imaging examination	Day 0
PET imaging examination	Intensity and topography of [18F]DPA-714-labeled microglial activation in vivo in PET imaging examination	Month 3

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Stein SILVA, MD, PhD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 4, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: delirium; COVID-19; microglial activation; SARS-CoV-2 neurotropism
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Trauma and Stressor Related Disorders; COVID-19; Delirium; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: RC31/20/0441; 2020-005827-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No