Neuro-PASCPASCNCT06932237
Immune-mediated Pathogenic Mechanisms of Neuro-PASC in Veterans
An observational study of Neuro-PASC and Long COVID, run by VA Office of Research and Development at 2 sites in United States.
Trial summary
Mental health symptoms, including cognitive impairment ("brain fog"), following COVID-19 are of great concern to Veterans. This 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuro-PASC, Long COVID
- How many people
- 200 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Feb 2025to 31 Mar 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Veterans
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Not yet recruiting
James H. Quillen VA Medical Center, Mountain Home, TN
Mountain Home, Tennessee, 37684
Jonathan Moorman, MD, 423-439-8065, jonathan.moorman@va.gov
- Recruiting
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97207-2964
Jennifer M Loftis, MA PhD, 503-220-8262 ext. 57155, Jennifer.Loftis2@va.gov
Emily R Sano, MA, (503) 220-8262 ext. 58290, emily.sano@va.gov
About this study
Mental health symptoms, including cognitive impairment ("brain fog"), following COVID-19 are of great concern to Veterans. This 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.
Read the 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.
- Conditions
- Neuro-PASC, Long COVID
- Keywords
- COVID-19, Veterans, Cognitive, Post-Acute COVID-19 Syndrome
- Medical subject headings
- Post-Acute COVID-19 Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Neuro-PASC | All participants enrolled in the study will attend 4 study visits: 1) Screening, 2) Baseline, 3) 6-Month Follow-up, and 4) 12-Month Follow-up. At the Baseline, 6-Month, and 12-Month follow-up, participants will complete an online neuropsychological assessment, questionnaires, blood draw, and saliva collection | |
| Neuro-PASC-imaging | A subset (60) of Portland VA only participants will be provided with the opportunity to complete an MRI visit at baseline and the 12-month follow-up. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Severity Scale (FSS)
A nine-item self-report questionnaire designed to assess fatigue as a symptom of a variety of different chronic conditions and disorders.
Measured: Baseline, 6-Month, 12-Month
Prospective and Retrospective Memory Questionnaire (PRMQ)
A self-report measure of everyday memory, assessing prospective (the ability to remember to do things in the future) and retrospective memory.
Measured: Baseline, 6-Month, 12-Month
Spatial Working Memory (SWM)
Online cognitive assessment requiring retention and manipulation of visuospatial information; measures executive functioning (i.e., strategy) and working memory.
Measured: Baseline, 6-Months, 12-Months
Paired Associates Learning (PAL)
Online cognitive assessment measuring visual memory and new learning.
Measured: Baseline, 6-Month, 12-Month
Stockings of Cambridge (SOC)
Online cognitive assessment measuring problem-solving strategies.
Measured: Baseline, 6-Month, 12-Month
Delayed Matching Sample (DMS)
Online cognitive assessment measuring visual matching ability and short-term visual recognition memory.
Measured: Baseline, 6-Month, 12-Month
Rapid Visual Information Processing (RVP)
Online cognitive assessment measuring sustained attention.
Measured: Baseline, 6-Month, 12-Month
Apolipoprotein E (APOE) Genotyping
A genetic test that determines a person's inherited variations in the APOE gene. This gene plays a role in cholesterol metabolism and brain health. Blood and saliva samples will be used.
Measured: Baseline, 6-Months, 12-Months
Long Covid Questionnaire
Self-report measure that assesses the continued presence of Long-COVID symptomology.
Measured: Baseline
Delis-Kaplan Executive Functioning - Verbal Fluency (D-KEFS-VF)
Neuropsychological assessment measure of verbal behavioral productivity and cognitive flexibility.
Measured: Baseline, 6-Months, 12-Months
Secondary outcomes (4)
Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C)
A standardized self-report rating scale for PTSD comprising 17 items that correspond to the key symptoms of PTSD.
Measured: Baseline, 6-Month, 12-Month
Patient Health Questionnaire-9 (PHQ-9)
Self-report questionnaire objectifying and assessing degree of depression severity.
Measured: Baseline, 6-Months, 12-Months
Generalized Anxiety Disorder-7 (GAD-7)
A self-reported questionnaire used to assess the severity of anxiety symptoms.
Measured: Baseline, 6-Month, 12-Month
Biomarkers
Obtained from collected blood samples and saliva, biomarkers (including viral variants, genetic susceptibility, inflammatory markers, diagnostic markers, etc.) associated with specific symptoms of post-COVID conditions will be identified.
Measured: Baseline, 6-Months, 12-Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2025
- Study start20 Feb 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuro-PASCStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- James H. Quillen Department of Veterans Affairs Medical Center
- Responsible party
- Sponsor
- Investigators
- Jennifer M Loftis, MA PhD, Principal investigator, VA Portland Health Care System, Portland, OR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06932237
- Sponsor's protocol ID
- MHBC-006-23S
- Other IDs
- I01CX002668
- Acronym
- PASC
- Status last verified
- Mar 2026
- First submitted
- 9 Apr 2025
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune-mediated Pathogenic Mechanisms of Neuro-PASC in Veterans
- ClinicalTrials.gov ID
- NCT06932237
- Acronym / sponsor ID
- PASC / MHBC-006-23S
- Conditions
- Neuro-PASC, Long COVID
- Keywords
- COVID-19, Veterans, Cognitive, Post-Acute COVID-19 Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- James H. Quillen Department of Veterans Affairs Medical Center
- Study start
- 20 Feb 2025 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 17 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mental health symptoms, including cognitive impairment ("brain fog"), following COVID-19 are of great concern to Veterans. This 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neuro-PASC | – | –All participants enrolled in the study will attend 4 study visits: 1) Screening, 2) Baseline, 3) 6-Month Follow-up, and 4) 12-Month Follow-up. At the Baseline, 6-Month, and 12-Month follow-up, participants will complete an online neuropsychological assessment, questionnaires, blood draw, and saliva collection |
| Neuro-PASC-imaging | – | –A subset (60) of Portland VA only participants will be provided with the opportunity to complete an MRI visit at baseline and the 12-month follow-up. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Veterans
Key inclusion criteria (5 listed)
- 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
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Fatigue Severity Scale (FSS)
Time frame: Baseline, 6-Month, 12-Month
A nine-item self-report questionnaire designed to assess fatigue as a symptom of a variety of different chronic conditions and disorders.
Prospective and Retrospective Memory Questionnaire (PRMQ)
Time frame: Baseline, 6-Month, 12-Month
A self-report measure of everyday memory, assessing prospective (the ability to remember to do things in the future) and retrospective memory.
Spatial Working Memory (SWM)
Time frame: Baseline, 6-Months, 12-Months
Online cognitive assessment requiring retention and manipulation of visuospatial information; measures executive functioning (i.e., strategy) and working memory.
Paired Associates Learning (PAL)
Time frame: Baseline, 6-Month, 12-Month
Online cognitive assessment measuring visual memory and new learning.
Stockings of Cambridge (SOC)
Time frame: Baseline, 6-Month, 12-Month
Online cognitive assessment measuring problem-solving strategies.
Delayed Matching Sample (DMS)
Time frame: Baseline, 6-Month, 12-Month
Online cognitive assessment measuring visual matching ability and short-term visual recognition memory.
Rapid Visual Information Processing (RVP)
Time frame: Baseline, 6-Month, 12-Month
Online cognitive assessment measuring sustained attention.
Apolipoprotein E (APOE) Genotyping
Time frame: Baseline, 6-Months, 12-Months
A genetic test that determines a person's inherited variations in the APOE gene. This gene plays a role in cholesterol metabolism and brain health. Blood and saliva samples will be used.
Long Covid Questionnaire
Time frame: Baseline
Self-report measure that assesses the continued presence of Long-COVID symptomology.
Delis-Kaplan Executive Functioning - Verbal Fluency (D-KEFS-VF)
Time frame: Baseline, 6-Months, 12-Months
Neuropsychological assessment measure of verbal behavioral productivity and cognitive flexibility.
4 secondary outcomes
Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C)
Time frame: Baseline, 6-Month, 12-Month
Patient Health Questionnaire-9 (PHQ-9)
Time frame: Baseline, 6-Months, 12-Months
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: Baseline, 6-Month, 12-Month
Biomarkers
Time frame: Baseline, 6-Months, 12-Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Neuro-PASC
RecruitingPhase 1
PET Imaging of Cyclooxygenase-1 in Participants With Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
Long COVID, Post Acute Sequelae of COVID-19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jennifer M Loftis, MA PhD principal investigator
VA Portland Health Care System, Portland, OR
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neuro-PASC and Long COVID, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer M Loftis, MA PhD ((503) 220-8262 ext. 57155, Jennifer.Loftis2@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue Severity Scale (FSS) (time frame: Baseline, 6-Month, 12-Month). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026; AzTrials last refreshed its copy on 8 Nov 2026.