Mental health symptoms, including cognitive impairment ("brain fog"), following COVID-19are of great concern to Veterans. The investigators' research seeks to advanceunderstanding of the long-term effects of COVID-19 on neuropsychiatric and neurologicalfunctions, identifying clinically relevant biomarkers and directions for developing andtesting therapeutic interventions. To accomplish these objectives the investigators areconducting a longitudinal study at two VA medical centers to: 1) assess and monitorcognitive function and psychiatric symptoms in Veterans post-COVID; 2) evaluatebiomarkers of inflammation and signaling pathways associated with viral infection andneuropsychiatric function; and 3) integrate neuropsychiatric and neurological findingswith biological data to identify biomarkers and clinical endpoints associated withdisease progression or severity, as well as those for promoting brain repair andattenuating those symptoms.
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.
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
VA Portland Health Care System, Portland, OR
Portland, Oregon, United States
James H. Quillen VA Medical Center, Mountain Home, TN
Mountain Home, Tennessee, United States
Jennifer M Loftis, MA PhD
503-220-8262 - 57155
Jennifer.Loftis2@va.gov
Emily R Sano, MA
(503) 220-8262 - 58290
emily.sano@va.gov
Jennifer M Loftis, MA PhD, Principal Investigator
VA Portland Health Care System, Portland, OR