Neuropsychiatric Post-Acute Sequelae of SARS-CoV-2 (PASC) Using TSPO Positron Emission Tomography (PET) and MRI

NCT05615415 | Active Not Recruiting FDA Drug FDA Device

• 1 other identifier: 21-00945
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching goal of this study is to develop PET/MR techniques for the diagnosis of neuropsychiatric post-acute sequelae (PASC) of SARS-CoV-2. The central hypothesis is that immunological and cerebrovascular dysfunction after acute SARS-CoV-2 infections mediate neuropsychiatric PASC (NP-PASC).

Conditions

Neuropsychiatric Post-Acute Sequelae of SARS-CoV-2 Infection

Keywords

Long COVID; COVID-19; Cognitive Deficit Following COVID-19; Depression and Anxiety following COVID-19

Outcome Measures

Primary Outcomes (10)

• Level of Translocator Protein (TSPO)

  Binding of PET tracer to TSPO.

  PET/MR Visit (Day 1)

• Occurrence of Microhemorrhages

  Evaluated using MRI images (Susceptibility Weighted MRI (SWI), Fluid Attenuated Inversion Recovery (FLAIR), Diffusion Weighted Imaging (DWI), and anatomical MRI).

  PET/MR Visit (Day 1)

• Permeability Surface Area Product (PS)

  Used to evaluate disruptions in the blood-brain-barrier. Derived from the DCE-MRI.

  PET/MR Visit (Day 1)

• Cerebral Blood Flow

  Evaluated using cerebral blood flow maps from Arterial Spin Labeling (ASL).

  PET/MR Visit (Day 1)

• Peripheral Levels of Pro-Inflammatory Cytokines

  Evaluated using blood samples.

  PET/MR Visit (Day 1)

• Peripheral Levels of High-Sensitivity C-reactive Protein (hs-CRP)

  Evaluated using blood samples.

  PET/MR Visit (Day 1)

• CSF Levels of Pro-Inflammatory Cytokines

  Evaluated using cerebrospinal fluid collection (optional procedure).

  CSF Visit (Screening) (Optional)

• CSF Levels of High-Sensitivity C-reactive Protein (hs-CRP)

  Evaluated using cerebrospinal fluid collection (optional procedure).

  CSF Visit (Screening) (Optional)

• Free Diffusing Water Fraction

  Calculated using DWI.

  PET/MR Visit (Day 1)

• Extra-Axonal Water Fraction

  Calculated using DWI.

  PET/MR Visit (Day 1)

Study Arms (2)

NP-PASC (neuropsychiatric post-acute sequelae of SARS-CoV-2)

Individuals with new onset a) cognitive and/or b) psychiatric symptoms following SARS-CoV-2 infection. Participants will undergo PET/MR scanning, during which a TSPO PET tracer and a Gadolinium-based MRI tracer will be administered intravenously and blood samples will be collected from an arterial line. In addition, blood samples will be taken at screening. Participants can elect to provide an optional cerebrospinal fluid (CSF) sample.

Drug: PET Tracer; Drug: MRI Tracer; Device: 3T PET/MRI

CC (COVID Control)

Individuals with a history of SARS-CoV-2 infection who do not meet the criteria for any DSM-5 diagnosis and perform within normal limits on cognitive tests. Participants will undergo PET/MR scanning, during which a TSPO PET tracer and a Gadolinium-based MRI tracer will be administered intravenously and blood samples will be collected from an arterial line. In addition, blood samples will be taken at screening. Participants can elect to provide an optional cerebrospinal fluid (CSF) sample.

Drug: PET Tracer; Drug: MRI Tracer; Device: 3T PET/MRI

Interventions

PET Tracer DRUG

Standard radiopharmaceutical injected via intravenous catheter during PET-MR scanning.

Also known as: C11-ER176

CC (COVID Control); NP-PASC (neuropsychiatric post-acute sequelae of SARS-CoV-2)

MRI Tracer DRUG

Injected via intravenous catheter during PET-MR scanning.

Also known as: Gadolinium-Based Contrast Agent (GBCA)

CC (COVID Control); NP-PASC (neuropsychiatric post-acute sequelae of SARS-CoV-2)

3T PET/MRI DEVICE

Used to evaluate neuroinflammation and cerebrovascular measures. Some MRI image acquisitions will employ work in progress (WIP) sequences, including ASL (Arterial Spin Labeling), Diffusion and T2-weighted EPI (DT2W), Golden-angle radial sparse parallel (GRASP) DCE-MRI, and Magnetization Transfer (MT) imaging.

CC (COVID Control); NP-PASC (neuropsychiatric post-acute sequelae of SARS-CoV-2)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The population will include neuropsychiatric PASC patients, as well as patients with a history of SARS-CoV-2 but no NP-PASC. Potential participants may be directly identified, referred through the ongoing PASC projects at NYU Neurology, identified by the NYU Radiology research coordinators, or recruited via ads. Recruitment will strive to match the two groups in age, sex and BMI.

You may qualify if:

• Neuropsychiatric symptoms are defined as respectively a) objective cognitive dysfunction on bedside cognitive testing (ACE-III (Addenbrooke's Cognitive Examination III) =\< 86/100, at least 12th grade educational level), and/or b) anxiety, depression or psychotic illness as indicated by the DSM-5 diagnostic criteria, evaluated with the MINI (Mini International Psychiatric Interview) or SCID-5 (Structured Clinical Interview for DSM-5 Disorders, Research Version). It is expected some patients may fall into both categories (cognitive and psychiatric complications), in which case they will be included in this study.
• Infection with SARS-CoV-2 (3-12 months before study) will be verified based on positive PCR test results provided by the NYU EMR or subject records. Investigators will further record the clinical history and perform nucleoprotein- and spike-antibody testing. Anecdotal evidence shows that anti-nucleoprotein and anti-spike tests will be positive in individuals who had past SARS-CoV-2 infection, but only anti-spike tests will be positive in individuals who were vaccinated but did not have past infection, unless the infected individual has already lost the antibodies due to natural infection .
• Able to sign informed consent as evaluated by the UCSD Brief Assessment of Capacity to Consent (UBACC) test.
• NP-PASC subjects will have new onset a) cognitive and/or b) psychiatric symptoms following SARS-CoV-2 infection.
• CC will have a history of SARS-CoV-2 infection but will not meet the criteria for any DSM-5 diagnosis and will perform within normal limits on cognitive tests.

You may not qualify if:

• If vaccinated for SARS-CoV-2, at least 3 months past the last vaccine administration.
• Subjects with suicidal ideation who require inpatient or intensive level of care, as determined by a study clinician (Dr. Frankle or Dr. Iosifescu) based on the answers to the screening interview. These patients will be immediately referred to appropriate clinical treatment.
• Pregnant women or those who become pregnant as determined by a urine test at the time of the blood test and on the day of the PET/MR scan.
• Obese individuals (BMI \>= 30) and individuals with cardiovascular risk factors (e.g., uncontrolled high blood pressure, hypercholesterolemia, current tobacco smokers or smoking in the last 12 months, diabetes mellitus).
• Individuals with history of serious or unstable medical illness associated with chronic inflammation other than PASC (e.g., rheumatoid arthritis, SLE, etc).
• Clinical or laboratory evidence of hypothyroidism. A thyroid stimulating hormone (TSH) test will be drawn in blood, and the patient will be excluded if TSH is abnormal.
• Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding baseline.
• Subjects who had recently taken psychotropic medications will be scanned only after a period greater than five half-lives since the last dose of their psychotropic medication. Subjects who choose to start treatment (with psychotropic medication) for their symptoms immediately will thus be excluded.
• Contraindications to 3T whole body MRI scanners (e.g., pacemaker, cerebral aneurysm clip, cochlear implant, presence of shrapnel in strategic locations, metal in the eye, claustrophobia, or other problems).
• Contraindications for Gadolinium-based MRI contrast (allergies to contrast agents and kidney health)
• Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits of 5 rem per 12 months as confirmed by the Radiation safety questionnaire.
• If CSF sampling: contraindication for a lumbar puncture (i.e. intracranial mass, bleeding diathesis, spinal developmental anomalies, or local skin infection involving the lower back). Complete blood count and coagulation studies will be drawn, and if abnormal (INR\>1.3, platelets less than 100), subjects will be able to complete imaging studies but will not be eligible for the lumbar puncture procedure part of the study.
• Unable to sign informed consent or to comply with study assessments.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19; Depression

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Steven Baete

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 14, 2022
• Study Start: February 15, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: Requests should be directed to Steven.baete@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)