Neuroinflammation in COVID-19 and Depression

Imaging Neuroinflammation in COVID-19 and Persistent Depression With/Without Other Neuropsychiatric Symptoms

The purpose of this study is to use state of the art brain imaging technology to investigate neuroinflammation in participants with depression after the respiratory symptoms of coronavirus disease 2019 (COVID-19) have passed.

Study Overview

• Status: Completed
• Conditions: Covid19; Major Depressive Episode
• Intervention / Treatment: Other: [18F]FEPPA PET scan; Other: [11C]SL25.1188 PET scan

Detailed Description

Participants will undergo two positron emission tomography (PET) scans: one [18F]FEPPA scan (for translocator protein (TSPO)) and one [11C]SL25.1188 scan (for monoamine oxidase B (MAO-B)) - as well as one magnetic resonance imaging (MRI) scan.

The primary hypotheses are:

1. TSPO total distribution volume (TSPO VT) and MAO-B total distribution volume (MAO-B VT) are greater in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampus in COVID-19 with new onset, persistent major depressive episode (MDE) with or without other neuropsychiatric symptoms after recovery from mild respiratory symptoms (DNP-mild).
2. TSPO VT and MAO-B VT are greater in the PFC, ACC, and hippocampus in COVID-19 with new onset, persistent MDE with or without other persistent neuropsychiatric symptoms after recovery from moderate respiratory symptoms (DNP-moderate).

Exploratory hypotheses are:

1. Greater TSPO VT and MAO-B VT in the PFC, ACC, and hippocampus will be positively associated with severity of MDE symptoms and poorer performance on cognitive tasks.
2. TSPO VT and MAO-B VT will be positively correlated in the PFC, ACC and hippocampus in COVID-DNP.

• Study Type: Observational
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants that have recovered from mild or moderate COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).

Description

Inclusion Criteria:

• Age 18 to 80
• Diagnosis of COVID-19
• Recovered from mild or moderate COVID-19 symptoms. Mild is defined as no evidence of pneumonia or hypoxia. Moderate is defined as presence of clinical symptoms of pneumonia but not severe enough to require ongoing use of supplementary oxygen.
• Recovered from physical COVID-19 symptoms including cough, shortness of breath, fever, chills, or gastrointestinal upset for at least 4 weeks
• New onset major depressive episode (MDE) within 3 months after COVID-19, as verified by the Research Version of Structured Clinical Interview for DSM 5 (SCID-5-RV)
• High-affinity-binder (HAB) or mixed-affinity-binder (MAB) genotype for rs6971 polymorphism, based on saliva genetic testing

Exclusion Criteria:

• Lifetime history of an autoimmune disease
• Lifetime history of a neurological disease, excluding migraine
• Lifetime diagnosis of Antisocial or Borderline Personality disorder
• Lifetime history of psychotic symptoms prior to COVID-19
• Lifetime diagnosis of Substance of Alcohol Use Disorder
• Use of street drugs, including marijuana, in the past two months
• Presence of cigarette smoking in the past two months
• Positive urine drug or cotinine screen at any timepoint during the study
• Currently pregnant
• Currently breastfeeding
• Use of aspirin or ibuprofen within the past 2 weeks
• Use of any other anti-inflammatory medication or MAO-B inhibitors within the past 4 weeks
• Use of herbal remedies in the past month
• Presence of metal implant, object or electrical devices that are contraindicated for MRI
• Current disorders of coagulation, blood or ongoing use of anticoagulant medication
• Claustrophobia
• Weight over 400lbs and height over 7ft
• History of undergoing a number of PET scans that will lead participants to exceed the annual (20mSv) / lifetime (8 PET scans) radiation by completing this study
• Current participation in another research study

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DNP-mild; Participants that have recovered from mild COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).	Other: [18F]FEPPA PET scan; One [18F]FEPPA PET for TSPO VT, and one MRI scan; Other: [11C]SL25.1188 PET scan; One [11C]SL25.1188 PET scan for MAO-B VT, and one MRI scan
DNP-moderate; Participants that have recovered from moderate COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).	Other: [18F]FEPPA PET scan; One [18F]FEPPA PET for TSPO VT, and one MRI scan; Other: [11C]SL25.1188 PET scan; One [11C]SL25.1188 PET scan for MAO-B VT, and one MRI scan
Healthy Control Participants; Participants in good physical health, age- and sex-matched to Group 1 and 2 participants.	Other: [18F]FEPPA PET scan; One [18F]FEPPA PET for TSPO VT, and one MRI scan; Other: [11C]SL25.1188 PET scan; One [11C]SL25.1188 PET scan for MAO-B VT, and one MRI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Translocator protein total distribution volume in prefrontal cortex, anterior cingulate cortex, and hippocampus	PET scan measures in DNP-mild and DNP-moderate compared to healthy controls	within 3 to 4 weeks after initiation of screening
Monoamine oxidase B total distribution volume in prefrontal cortex, anterior cingulate cortex, and hippocampus	PET scan measures in DNP-mild and DNP-moderate compared to healthy controls	within 3 to 4 weeks after initiation of screening

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Jeffrey H Meyer, M.D., PhD, Brain Health Imaging Centre, Centre for Addiction and Mental Health (CAMH)

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2021
• Primary Completion (Actual): December 21, 2023
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Inflammation; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Neuroinflammatory Diseases
• Other Study ID Numbers: 177/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No