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Principal Investigator: PAUL E SCHULZ
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
Fiscal Year: 2024
Award: $639,692
Funding agency: National Institute on Aging
PROJECT SUMMARY/ABSTRACT
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, which causes Coronavirus Disease
2019 (COVID-19), has become a global health crisis. To date, more than 6.5 million deaths from COVID-19 have
been reported worldwide. Amongst survivors, neurocognitive dysfunction and neuropsychiatric disorders, such
as anxiety and depression, are increasingly recognized and can persist for months, or even years. This enduring
neurocognitive and neuropsychiatric distress obligates us to address critical questions about their duration, risk
factors, and underlying mechanisms. The goal of this project is to test the hypothesis that SARS-CoV-2 promotes
cognitive decline in subjects who were previously normal via stimulating inflammatory pathways, with the
greatest risk being in older adults, females, and those from underrepresented groups. We propose to utilize
patients in our biorepository, who were hospitalized with SARS-CoV-2 infection, to achieve three Specific Aims:
(1) to determine the type and duration of neurocognitive dysfunction present; (2) to ascertain risk factors for
ongoing cognitive decline, including sex, age, race/ethnicity and comorbidities; and, (3) to verify that persistent
neuroinflammation underlies cognitive decline. To achieve these Aims, our team has established a well-curated,
highly diverse biorepository of more than 650 patients hospitalized with COVID-19. About 15% have succumbed
to COVID-related illnesses; however, 37% have continued to return for testing at 3-6 and 12-months post
hospitalization. Preliminary data demonstrates that 30% of subjects returning at one year show progressive
cognitive decline, which is associated with elevated markers of inflammation and neuronal stress. Here we
propose to follow these patients and perform detailed cognitive testing and assess biomarkers from their blood-
serum, spinal fluid, and imaging to explicate the type and time course of cognitive changes present, the risk
factors associated with cognitive dysfunction, and whether inflammation-induced neuronal distress underlies
progressive neurocognitive impairment. This proposal is innovative because we are evaluating the long-term
neurocognitive consequences of severe COVID-19 from a cohort that we have followed since the onset of the
pandemic, which has provided preliminary data supporting our Aims. Moreover, we have brought together
investigators with expertise in cognitive assessment and treatment, and basic and translational research, all in
the setting of a strong institutional infrastructure. Our work is significant because understanding the role of
persistent neuroinflammation in COVID-19-induced cognitive dysfunction will greatly enhance our ability to
rationally test immunosuppressants for this very debilitating disorder.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Affective Disorders><Age><Anatomic Sites><Anatomic structures><Anatomy><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Anxiety><Apoplexy><Attention><Basic Research><Basic Science><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Serum><Brain Vascular Accident><COVID-19><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 death><COVID-19 fatality><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 induced neurocognitive dysfunction><COVID-19 infection><COVID-19 mortality><COVID-19 neurocognitive consequences><COVID-19 neurocognitive impacts><COVID-19 neurocognitive manifestations><COVID-19 neurocognitive sequelae><COVID-19 related cognitive decline><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 virus><COVID-19 virus infection><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 death><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 virus><CV-19><Cerebral Stroke><Cerebrospinal Fluid><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Characteristics><CoV-2><CoV2><Cognition Therapy><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive Psychotherapy><Cognitive Therapy><Cognitive decline><Cognitive function abnormal><Cognitive treatment><Coronavirus Infectious Disease 2019><Data><Development><Disease><Disorder><Distress><Disturbance in cognition><Dysfunction><Ethnic Origin><Ethnicity><Exhibits><Female><Functional disorder><Functional impairment><Goals><Hospital Admission><Hospitalization><Hospitals><IGIV><IQ Deficit><IV Immunoglobulins><IVIG><Image><Immune globulin IV><Immunoglobulin Therapy><Immunosuppressants><Immunosuppressive Agents><Immunosuppressive drug><Immunosuppressive treatment><Impaired cognition><Induced Neurons><Infection><Inflammation><Inflammatory><Infrastructure><Institution><Intervention><Intervention Strategies><Intravenous Antibodies><Intravenous IG><Intravenous Immune Globulin><Intravenous Immunoglobulins><Investigators><Lead><Learning><Link><Medical><Medical Records><Memory><Mental Depression><Mood Disorders><Nerve Cells><Nerve Unit><Neural Cell><Neurocognitive><Neurocognitive Deficit><Neurocyte><Neurologic><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurological><Neurological Manifestations><Neurological Signs and Symptoms><Neurons><Neuropsychologic Tests><Neuropsychological Tests><PET><PET Scan><PET imaging><PETSCAN><PETT><Participant><Pathway interactions><Patients><Pb element><Peripheral><Persons><Physiopathology><Plasma Exchange><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Probability><QOL><Quality of life><Race><Races><Rad.-PET><Reporting><Research Personnel><Researchers><Risk><Risk Factors><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 fatality><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced mortality><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 neurocognitive sequelae><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Screening procedure><Serum><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Stress><Stroke><Survivors><Testing><Thick><Thickness><Time><Translational Research><Translational Science><Underrepresented Groups><Underrepresented Populations><Work><Wuhan coronavirus><age associated effects><age effect><age related effects><ages><aging effect><bio-markers><biobank><biologic marker><biomarker><biorepository><brain attack><brain size><cerebral spinal fluid><cerebral vascular accident><cerebrovascular accident><co-morbid><co-morbidity><cognitive assessment><cognitive behavior intervention><cognitive behavior modification><cognitive behavior therapy><cognitive behavioral intervention><cognitive behavioral modification><cognitive behavioral therapy><cognitive behavioral treatment><cognitive change><cognitive dysfunction><cognitive loss><cognitive testing><cohort><comorbidity><compare to control><comparison control><coronavirus disease 2019><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated mortality><coronavirus disease 2019 death><coronavirus disease 2019 fatality><coronavirus disease 2019 induced death><coronavirus disease 2019 induced fatality><coronavirus disease 2019 induced mortality><coronavirus disease 2019 infection><coronavirus disease 2019 mortality><coronavirus disease 2019 related death><coronavirus disease 2019 related fatality><coronavirus disease 2019 related mortality><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 mortality><coronavirus disease-19 virus><coronavirus infectious disease-19><death due to COVID-19><death due to COVID19><death due to SARS-CoV-2><death due to coronavirus disease 2019><death due to severe acute respiratory syndrome coronavirus 2><death in COVID><death in COVID-19><death in SARS-CoV-2><death in coronavirus disease><death in coronavirus disease 2019><death in severe acute respiratory syndrome coronavirus 2><depression><developmental><digital><elderly patient><executive control><executive function><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><global health><gray matter><hCoV19><heavy metal Pb><heavy metal lead><iNeuron><imaging><immune suppressive agent><immune suppressor><immunosuppressive substance><immunosuppressor><impact of age><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><infection rate><inflammation marker><inflammatory marker><influence of age><innovate><innovation><innovative><intelligence quotient deficit><intervention design><interventional strategy><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><mortality due to COVID-19><mortality due to COVID19><mortality due to SARS-CoV-2><mortality due to coronavirus disease 2019><mortality due to severe acute respiratory syndrome coronavirus 2><nCoV2><neural inflammation><neural manifestation><neurocognitive decline><neurocognitive impairment><neurocognitive outcomes of coronavirus disease-19><neurocognitive symptoms and sequelae during COVID-19><neuroinflammation><neuroinflammatory><neuronal><neuropsychiatric><neuropsychiatric disease><neuropsychiatric disorder><neuropsychiatry><older adult><older adulthood><older patient><p-tau><p-τ><pandemic><pandemic disease><participant enrollment><pathophysiology><pathway><patient enrollment><phospho-tau><phospho-τ><phosphorylated tau><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><post COVID cognitive impairment><post-COVID><post-COVID-19><post-coronavirus disease 2019><post-translational modification of tau><posttranslational modification of tau><processing speed><prospective><racial><racial background><racial origin><rate of infection><screening><screening tools><screenings><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 associated death><severe acute respiratory syndrome coronavirus 2 associated fatality><severe acute respiratory syndrome coronavirus 2 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groups><under represented groups><under represented people><under represented populations><underrepresentation of groups><underrepresented people><verbal><τ phosphorylation>