Project Summary
In the USA, SARS-CoV-2 has infected more than 16 million children and adolescents, who are undergoing critical
periods of brain development when higher cognitive abilities are acquired, and mental illnesses typically emerge.
Autopsy, blood, and CSF studies during acute COVID-19 reported neuroinflammation, which can alter cerebral
white and gray matter morphometry, microstructure, and brain function. These brain alterations are associated
with elevated risks for cognitive deficits and mental illness. A major gap in our current knowledge exists in
understanding how SARS-CoV-2 infection during adolescence may impact brain structure and function and
consequently, cognition and mental health. To address this gap, we will utilize pre-/post-pandemic neuroimaging,
cognitive, and psychiatric symptom data from the Adolescent Brain Cognitive Development (ABCD) Study®. We
will test the overall hypothesis that neuroinflammation during acute SARS-CoV-2 infection leads to brain
changes that are detectable on MRI, including lasting alterations in macro and microstructural and
functional abnormalities, which in turn mediate poorer cognitive performance and mental health. In Aim
1, we will identify morphometric (on structural MRI) and microstructural (on diffusion tensor imaging)
abnormalities associated with SARS-CoV-2 infection by comparing longitudinal MRI data between those with
(COVID+) and without a prior documented COVID-19 history (COVID-) to evaluate group differences on cortical
thickness, cortical surface areas, subcortical volumes, and microstructural measures across baseline, year 2
and year 4 follow-up visits. Aim 2 will determine whether SARS-CoV-2 infection alters brain function using the
Emotional N-Back task. We will longitudinally compare brain activation patterns and performance scores
between the COVID+ and COVID- groups. Aim 3 will evaluate whether SARS-CoV-2 infection is associated with
increased risks for neurobehavioral abnormalities. We will use data from the NIH Toolbox® Cognitive Battery
and Kiddie Schedule for Affective Disorders and Schizophrenia 5 to longitudinally compare cognitive
performance and anxiety/depression prevalence between the two groups. Lastly, mediation analyses will be
performed to assess the direct and indirect impact of changes in brain structure and function on cognition and
mental health. For all Aims, sex differences and sex-specific effects will be evaluated. Throughout this 3-year
project, I will be supported by my sponsor, Dr. Linda Chang, and my co-sponsors, Drs. Amal Isaiah, Gloria
Reeves, and Thomas Ernst, who will provide interdisciplinary expertise and training to me in the areas of COVID-
19, neuroimaging, neurodevelopment, cognitive assessments, clinical research, MRI data processing and
analyses, data mining, and adolescent psychiatry. Furthermore, my training will be sufficiently supplemented
with coursework, seminars, career workshops, conferences, and mentorship opportunities to allow me to fully
develop into a well-rounded, independent investigator in clinical neuroimaging research.