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Principal Investigator: KEJAL KANTARCI
Organization: UNIVERSITY OF MINNESOTA
Fiscal Year: 2024
Award: $615,261
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY/ABSTRACT
Since the World Health Organization declared COVID-19 a pandemic in March 2020, increasing
evidence has shown that the disease affects multiple organs, including the central nervous system (CNS).
Effects of COVID-19 on the CNS in the acute phase were documented clinically, by magnetic resonance
imaging (MRI) and spectroscopy (MRS), by plasma biomarkers and at autopsy, with neurological symptoms
manifesting in 1/3 to 2/3 of hospitalized, severe cases. After the acute phase, approximately 10% of patients
experience prolonged illness, during which neurological symptoms (headaches, cognitive blunting, and fatigue)
are among the top 10 symptoms reported by COVID-19 survivors. The underlying biology of these prolonged
symptoms is unknown; therefore, prospective studies to systematically investigate the pathophysiology of such
sequelae are urgently needed.
Based on the clinical presentation of COVID-19, reports of COVID-related symptoms in the months
following the infection, including reports of Parkinsonism and other delayed neurological and neurocognitive
complications ranging from mild-to-severe, and known peripheral triggers of cerebral pathology,
neuroinflammation (Aim 1), neurodegeneration (Aim 2) and cerebrovascular disease (CVD) (Aim 3) are
expected to be important components of long-term CNS pathophysiology.
The COVID BRain Advanced Imaging Network (COVID-BRAIN) was formed as a Consortium of six
institutions to systematically and prospectively elucidate the long-term CNS pathophysiology of COVID-19
using highly sensitive, harmonized, advanced MRI/MRS technology at 3 tesla in conjunction with standardized
neurological and neuropsychological evaluation and inflammatory blood biomarkers. Five sites that currently
partner in other multi-site neuroimaging initiatives (University of Minnesota, Mayo Clinic Rochester, Harvard
University/Massachusetts General Hospital, Johns Hopkins University, Houston Methodist Research Institute)
will collect longitudinal multi-modal MRI (T1, FLAIR, diffusion MRI, susceptibility-weighted MRI, single- and
multi-voxel MRS and pseudo-continuous arterial spin labeling), clinical, neurocognitive and blood biomarker
data from laboratory confirmed post-COVID cases with neurological symptoms (N=200) and matched controls
(N=100). The Laboratory of Neuro Imaging (LONI) at the University of Southern California will serve as the
data management site. Group differences and change over time in MR markers indicative of
neuroinflammation, neurodegeneration, hypoxia/ischemia and CVD and their associations with specific
neurological symptoms, cognitive function, and inflammatory blood biomarkers will be investigated.
The mechanistic insights provided by this study will inform the care and treatment of patients that are
expected to suffer long-term consequences of the pandemic for the years to come.
Terms: <(TNF)-α><Acute><Affect><Aging><Anisotropy><Antibodies><Atrophic><Atrophy><Autopsy><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Basal Ganglia><Basal Nuclei><Biochemical><Biological><Biological Markers><Biology><Biomedical Engineering><Bleeding><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Vessels><Brain><Brain Hypoxia-Ischemia><Brain Nervous System><Brain Vascular><Brain Vascular Disorders><CNS Nervous System><CNS infection><COVID survivors><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 effect><COVID-19 impact><COVID-19 impacted><COVID-19 infection><COVID-19 infection survivors><COVID-19 neural sequela><COVID-19 sequelae><COVID-19 survivors><COVID-19 virus infection><COVID19 infection><CV-19><Cachectin><California><Caring><Central Nervous System><Central Nervous System Infections><Central Nervous System Infectious Disease><Central Nervous System Infectious Disorder><Cephalalgia><Cephalgia><Cephalodynia><Cerebellum><Cerebrovascular Circulation><Cerebrovascular Disease><Cerebrovascular Disorders><Cerebrum><Choline><Clinic><Clinical><Cognitive><Cognitive deficits><Consensus><Coronavirus Infectious Disease 2019><Cranial Pain><DWI (diffusion weighted imaging)><DWI-MRI><Data><Degenerative Neurologic Disorders><Demyelinations><Deposit><Deposition><Diffusion><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Disease><Disorder><Dysfunction><Encephalon><Enrollment><Evaluation><Fatigue><Fe element><Functional disorder><Funding><General Hospitals><Gln><Glutamates><Glutamine><Goals><Guidelines><HPGF><Head Pain><Headache><Hemorrhage><Hepatocyte-Stimulating Factor><Hospital Admission><Hospitalization><Hybridoma Growth Factor><Hypoxia><Hypoxic><IFN-beta 2><IFNB2><IL-1><IL-6><IL1><IL6 Protein><Image><Imaging technology><Individual><Infarction><Infection><Inflammatory><Injury><Institution><Interleukin I><Interleukin-1><Interleukin-6><Intracranial Vascular Diseases><Intracranial Vascular Disorders><Investigation><Iron><Ischemia><L-Glutamate><L-Glutamine><Laboratories><Lack of Energy><Lesion><Leukoencephalopathy><Long-Term Effects><Longterm Effects><Lung><Lung Respiratory System><Lymphocyte-Stimulating Hormone><MGI-2><MR Imaging><MR Spectroscopy><MR Tomography><MRI><MRI biomarker><MRI marker><MRIs><Macrophage Cell Factor><Macrophage-Derived TNF><Magnetic Resonance Imaging><Magnetic Resonance Spectroscopy><Massachusetts><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Metabolic Diseases><Metabolic Disorder><Methodist Church><Methodists><Methodology><Minnesota><Monocyte-Derived TNF><Myeloid Differentiation-Inducing Protein><N-acetyl aspartate><N-acetyl-L-aspartate><N-acetylaspartate><NMR Imaging><NMR Tomography><Nerve Degeneration><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neuraxis><Neurocognitive><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic><Neurologic Degenerative Conditions><Neurologic Examination><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurological><Neurological Examination><Neurological Manifestations><Neurological Signs and Symptoms><Neuron Degeneration><Neuropsychologies><Neuropsychology><Nuclear Magnetic Resonance Imaging><Organ><Oxygen Deficiency><Parkinsonian><Parkinsonian Condition><Parkinsonian Diseases><Parkinsonian Disorders><Parkinsonian Syndrome><Parkinsonism><Participant><Pathologic><Pathology><Patients><Perfusion><Peripheral><Phase><Physiopathology><Plasma><Plasma Serum><Plasmacytoma Growth Factor><Predisposition><Prospective Studies><Q Levoglutamide><Q. Levoglutamide><Reporting><Research><Research Institute><Respiration Disorders><Respiratory Disorder><Respiratory Signs and Symptoms><Reticuloendothelial System, Serum, Plasma><SARS-CoV-2 infection><SARS-CoV-2 neurological sequelae><SARS-CoV-2 sequelae><SARS-CoV-2 survivors><SARS-CoV2 infection><Severe acute respiratory syndrome coronavirus 2 infection><Site><Spectroscopy><Spectrum Analyses><Spectrum Analysis><Standardization><Susceptibility><Symptoms><T Helper Factor><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Technology><Thesaurismosis><Time><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Underrepresented Ethnic Minority><Underrepresented Minority><Universities><Vaccines><Vendor><White Matter Hyperintensity><World Health Organization><Zeugmatography><airway symptom><arterial spin labeling><arterial spin tagging><astrogliosis><bio-engineered><bio-engineers><bio-markers><bioengineering><biologic><biologic marker><biological engineering><biomarker><blood flow in brain><blood loss><brain blood circulation><brain blood flow><brain vascular disease><brain vascular dysfunction><breathing disorder><cerebral><cerebral blood flow><cerebral circulation><cerebral vascular><cerebral vascular disease><cerebral vascular dysfunction><cerebro-vascular><cerebrocirculation><cerebrovascular><cerebrovascular blood flow><cerebrovascular dysfunction><chronic effect of COVID-19><chronic symptom><clinical trial readiness><cognitive defects><cognitive function><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 infection><coronavirus disease-19><coronavirus disease-19 impact><coronavirus infectious disease-19><dMRI><data management><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><demyelinate><develop therapy><diffused><diffuses><diffusing><diffusion tensor imaging><diffusions><enroll><experience><glutamatergic><head ache><high risk><hypoxia/ischemia><imaging><infarct><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammation marker><inflammatory marker><injuries><insight><interferon beta 2><intervention development><intracranial vascular dysfunction><long term consequences of COVID-19><long term consequences of SARS-CoV-2 infection><long term consequences of coronavirus disease-19><long term effects of COVID-19><long term health consequences of COVID-19><long term health consequences of SARS-CoV2 infection><long term impact of COVID-19><long term impact of SARS-CoV-2 infection><long-term consequence of severe acute respiratory distress syndrome-cov-2 infection><long-term effects of coronavirus disease-19><longterm consequences of COVID-19><longterm consequences of SARS-CoV-2 infection><longterm effects of COVID-19><longterm health consequences of COVID-19><longterm health consequences of SARS-CoV2 infection><longterm impact of COVID-19><longterm impact of SARS-CoV-2 infection><lymphocyte activating factor><magnetic resonance imaging biomarker><magnetic resonance imaging marker><metabolism disorder><multi-modality><multimodality><myoinositol><necropsy><nerve cell death><nerve cell loss><neural degeneration><neural imaging><neural inflammation><neural manifestation><neural sequela in COVID-19><neuro post-acute sequelae of SARS-CoV-2><neuro-imaging><neuroPASC><neurodegeneration><neurodegenerative><neurodegenerative illness><neuroimaging><neuroinflammation><neuroinflammatory><neurologic post acute sequelae of SARS-CoV-2><neurologic sequelae of COVID-19><neurological degeneration><neurological imaging><neurological post-acute sequelae of SARS-CoV-2><neurological sequelae associated with SARS-CoV-2><neurological sequelae caused by SARS-CoV-2><neuron cell death><neuron cell loss><neuron death><neuron loss><neuronal cell death><neuronal cell loss><neuronal death><neuronal degeneration><neuronal loss><neuropsychiatric><neuropsychiatry><neuropsychologic><non-invasive imaging><noninvasive imaging><pandemic><pandemic disease><pathophysiology><persistent symptom><post-COVID><post-COVID-19><post-acute CNS symptoms of SARS-CoV-2 infection><post-coronavirus disease 2019><postmortem><prospective><pulmonary><quantitative imaging><respiratory dysfunction><respiratory symptom><sequelae following COVID-19><sequelae following SARS-CoV-2 infection><sequelae of COVID-19><survive COVID-19><survive SARS-CoV-2><systemic inflammation><systemic inflammatory response><therapy development><treatment development><under-representation of minorities><under-represented minority><underrepresentation of minorities><vascular>