Clinical trial NCT06932237: Immune-mediated Pathogenic Mechanisms of Neuro-PASC in Veterans
Official title: Immune-mediated Pathogenic Mechanisms of Neuro-PASC in Veterans
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neuro-PASC
Long COVID
Keywords: COVID-19
Veterans
Cognitive
Post-Acute COVID-19 Syndrome
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: James H. Quillen Department of Veterans Affairs Medical Center
First posted: 2025-04-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Veterans

Brief summary: Mental health symptoms, including cognitive impairment ("brain fog"), following COVID-19 are of great concern to Veterans. The investigators' research seeks to advance understanding of the long-term effects of COVID-19 on neuropsychiatric and neurological functions, identifying clinically relevant biomarkers and directions for developing and testing therapeutic interventions. To accomplish these objectives the investigators are conducting a longitudinal study at two VA medical centers to: 1) assess and monitor cognitive function and psychiatric symptoms in Veterans post-COVID; 2) evaluate biomarkers of inflammation and signaling pathways associated with viral infection and neuropsychiatric function; and 3) integrate neuropsychiatric and neurological findings with biological data to identify biomarkers and clinical endpoints associated with disease progression or severity, as well as those for promoting brain repair and attenuating those symptoms.

Detailed description: The goal of this research project is to identify the neuroinflammatory mechanisms contributing to post-COVID cognitive deficits and neuropsychiatric symptoms \[neuro-PASC (post-acute sequelae of SARS CoV-2 infection)\]. This collaborative research effort will also characterize new or worsened mental health symptoms and genetic and environmental risk factors for the incidence and severity of post-COVID neuropsychiatric impairments. Aim 1 will monitor and evaluate cognitive injury and neuro-PASC symptoms and determine whether APOE genotype modulates severity of the cognitive injury and neuro-PASC symptoms. Cognitive functioning will be evaluated over time using neuropsychological measures assessing domains most relevant to PASC: learning and memory, attention/concentration, social cognition/emotions, and executive function; assessments will include standardized measures. Mental health symptoms known to be induced and exacerbated by inflammation and potentially developing as a result of COVID-19 will also be evaluated. APOE genotyping will be determined based on saliva or blood samples. Aim 2 will identify immune-related biomarkers associated with cognitive injury and neuro-PASC symptoms. Blood (plasma and cells) will be used to identify biomarkers associated with PASC progression or severity, promotion of brain repair, attenuation of symptoms. Plasma will be used for Olink proteomics, followed by confirmatory multiplex assays or enzyme-linked immunosorbent assays (ELISAs). The investigators will assess relationships among biomarkers and cognitive injury and neuro-PASC symptoms across APOE genotypes and contribute data and samples to the repository managed by Dr. Moorman (Co-Investigator). Aim 3 (exploratory aim; conducted in Portland only) will assess neuroimaging correlates of cognitive injury and neuro-PASC symptoms. Neuroimaging evaluations (i.e., whole brain voxel-based morphometry, diffusion-tensor imaging, resting-state connectivity, and task-based assessments) will be conducted at baseline and at 12 months to correlate magnetic resonance imaging (MRI) measures with symptoms of long COVID (e.g., cognitive impairment and neuropsychiatric symptoms) across APOE genotypes.

Eligibility criteria: Inclusion Criteria:

Eligible participants will:

* have a history of SARS-CoV-2 infection 4 weeks prior to enrollment, defined as a positive PCR or home antigen test
* be able to give informed consent as determined by brief cognitive exam and evaluation of understanding of the risks, benefits, and voluntary nature of the study

Additionally, participants enrolled as part of the neuro-PASC group must also:

* currently experience neuro-PASC symptoms, not present prior to infection, as confirmed by the "Long COVID-19 Symptom Assessment" scale, a self-report measure that consists of 46 common COVID-19 sequela symptoms

Exclusion Criteria:

Exclusion criteria for all groups:

* diagnosed with dementia, traumatic brain injury, a neurological syndrome (e.g. Parkinson disease, Alzheimer disease), or other progressive cognitive disorder before SARS-CoV-2 infection
* diagnosed with a mood or psychotic disorder before SARS-CoV-2 infection
* history of fibromyalgia or chronic fatigue syndrome prior to SARS-CoV-2 infection
* unstable medical conditions or active uncontrolled autoimmune or inflammatory conditions

Primary outcomes:
measure: Fatigue Severity Scale (FSS)
timeFrame: Baseline, 6-Month, 12-Month
measure: Prospective and Retrospective Memory Questionnaire (PRMQ)
timeFrame: Baseline, 6-Month, 12-Month
measure: Spatial Working Memory (SWM)
timeFrame: Baseline, 6-Months, 12-Months
measure: Paired Associates Learning (PAL)
timeFrame: Baseline, 6-Month, 12-Month
measure: Stockings of Cambridge (SOC)
timeFrame: Baseline, 6-Month, 12-Month
measure: Delayed Matching Sample (DMS)
timeFrame: Baseline, 6-Month, 12-Month
measure: Rapid Visual Information Processing (RVP)
timeFrame: Baseline, 6-Month, 12-Month
measure: Apolipoprotein E (APOE) Genotyping
timeFrame: Baseline, 6-Months, 12-Months
measure: Long Covid Questionnaire
timeFrame: Baseline
measure: Delis-Kaplan Executive Functioning - Verbal Fluency (D-KEFS-VF)
timeFrame: Baseline, 6-Months, 12-Months
Secondary outcomes:
measure: Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C)
timeFrame: Baseline, 6-Month, 12-Month
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Baseline, 6-Months, 12-Months
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: Baseline, 6-Month, 12-Month
measure: Biomarkers
timeFrame: Baseline, 6-Months, 12-Months
Other outcomes:
measure: Neuroimaging
timeFrame: Baseline, 12-Months
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
city: Mountain Home
country: United States
facility: James H. Quillen VA Medical Center, Mountain Home, TN
state: Tennessee
Study officials:
affiliation: VA Portland Health Care System, Portland, OR
name: Jennifer M Loftis, MA PhD
role: PRINCIPAL_INVESTIGATOR
References: