R01NS123445

Characterizing Persistent Subclinical Neurobehavioral Effects of COVID-19 in a Diverse Urban Population - Project Summary/Abstract

Excess cognitive dysfunction has been identified in older adult survivors of COVID-19, compared to other respiratory infections. SARS-CoV-2 may thus adversely impact the brain beyond what the cases of acute stroke, etc. suggest. Unrecognized brain effects of SARS-CoV-2 infection may impact current brain functioning and presage future neurodegeneration and overt neurologic dysfunction. However, absent known baseline functioning, detection of subclinical effects will be confounded by normal variation between cases and controls.

We will therefore leverage detailed pre-pandemic neurocognitive and imaging assessments to characterize subclinical effects on brain structure and function among a large cohort of younger patients who experienced mild or asymptomatic SARS-CoV-2 infection. We will identify 3 groups utilizing detailed serologic analysis and novel highly specific SARS-CoV-2 T-cell assays to allow confirmation of prior SARS-CoV-2 infection, even in the setting of COVID-19 vaccination:

(1) Mild COVID-19: 35 patients with laboratory confirmed COVID-19 who were not hospitalized;
(2) Asymptomatic: 35 with laboratory evidence of SARS-CoV-2 infection, but no history of COVID-19 symptoms;
(3) Controls: 70 matched individuals without laboratory or clinical evidence of prior SARS-CoV-2 infection.

All participants were healthy prior to COVID-19, with no comorbid risk factors or brain imaging abnormality and normal neurocognitive performance. Against this robust quantitative baseline, we will assess change due to SARS-CoV-2 infection by repeating a suite of neurological assessments, including brain imaging and assessments of neurocognitive function, mood, anxiety, stress, and social isolation due to the pandemic.

In addition to their pre-pandemic baseline, we will assess participants:
(1) At entry into this proposed study,
(2) 6 months after entry,
(3) 18 months after entry, and
(4) three years after entry, to address the following:

Aim 1 Brain Tissue Effects: Characterize change of macro/microstructure and functional connectivity from pre-pandemic, among SARS-CoV-2 infected patients and non-infected controls, over three years.

Aim 2 Functional Effects: Assess change in neurocognitive function from pre-pandemic, among SARS-CoV-2 patients, and in non-infected controls, over three years, while accounting for mood, stress, and social isolation.

Aim 3 Individual Risk Factors [Exploratory]: Explore whether individual characteristics, such as sex, BMI, SES, and race/ethnicity, modify the associations of SARS-CoV-2 infection with MRI and neurocognitive changes.

Confirming neurological morbidity in mild SARS-CoV-2 will have key implications for screening, care, and follow-up for brain dysfunction among those at risk. These problems would otherwise go unrecognized, despite potential for long-term, yet unrecognized morbidity. Our existing sample of previously healthy, young, ethnically diverse women and men from a high prevalence and high morbidity region, well-characterized prior to the COVID-19 pandemic, uniquely positions us to characterize subclinical brain injury and dysfunction due to SARS-CoV-2.

Albert Einstein College Of Medicine

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM; RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS; RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS; IMPROVED METHODS OF DISEASE PREVENTION; NEW METHODS OF DIAGNOSIS AND TREATMENT; DRUG DEVELOPMENT; DEVELOPMENT OF NEURAL DEVICES; CLINICAL TRIALS; AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH; SYNAPSE FORMATION, FUNCTION, AND PLASTICITY; LEARNING AND MEMORY; CHANNELS, TRANSPORTERS, AND PUMPS; CIRCUIT FORMATION AND MODULATION; BEHAVIORAL AND COGNITIVE NEUROSCIENCE; SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION; NEUROENDOCRINE SYSTEMS; SLEEP AND CIRCADIAN RHYTHMS; AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE; TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM; NEURODEGENERATIVE DISORDERS; MOVEMENT DISORDERS; BRAIN TUMORS; CONVULSIVE DISORDERS; INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM; IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS; DISORDERS RELATED TO SLEEP; AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE THE NEUROSCIENCE WORKFORCE, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM; TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Bronx, New York 10461 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 375% from $712,681 to $3,388,628.