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) M ild 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; and (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 (3) three years after entry, to address the following: Aim 1 Brain Tissue Effects: Characterize change of macro/microstructure and functional connectivity frompre- 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. Theseproblems 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.