Neurotropism and Neuroinflammation in COVID-19 Patients With Delirium.

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Covid19, Delirium, Post-traumatic Stress Disorder

Intervention / Treatment
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* Biological: serology testing profiles description
* Biological: immune response characterization
* Other: in vivo brain PET-TSPO acquisitions
* Other: brain MRI assessment
* Behavioral: neurocognitive assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| severe COVID-19 patients with delirium<br>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<br>* SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF)<br>* Other names: biomarkers;Biological: immune response characterization<br>* systemic and central immune response characterization , associated to the assessment of CNS damage biomarkers (peripheral blood and CSF)<br>Other: in vivo brain PET-TSPO acquisitions<br>* in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia)<br>Other: brain MRI assessment<br>* structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity)<br>Behavioral: neurocognitive assessment<br>* multi-domains neurocognitive assessment<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, delirium, microglial activation, SARS-CoV-2 neurotropism