Neurological Sequelae Associated with Post-Acute SARS-CoV-2 Infection (NEURO-PASC)

Introduction: Lingering cognitive, sleep, and mental health symptoms are some of the most commonly reported lingering symptoms >60 days after a SARS-CoV-2 infection, and have been associated with prolonged cytokine elevation in children and biomarkers of neurodegeneration in adults. We hypothesize that SARS-CoV-2 infection affects both short-term and long-term neurocognitive and mental health outcomes by differentially impacting brain structure and function through inflammation.

Objective: We aim to pair the existing collection of inflammation biomarkers in the RECOVER pediatric protocol with advanced neuroimaging to examine the impact of past infection and current inflammatory markers on brain structure, functional connectivity, and neurocognitive function.

Methods: We will enroll N=150 Tier 2 post-acute participants, aged 7-19, from the VCU hub of the Pediatric RECOVER cohort. A non-RECOVER cohort of N = 90 historical, matched controls, recruited prior to COVID, will serve as the comparison group. Additional neuroimaging data collection, in addition to the Tier 3 protocol, includes Multi-Echo fMRI imaging to represent the brain's functional activity over time. An additional PAXGene RNA tube is also collected for T-cell repertoire sequencing, Whole blood RNA-seq, T-cell alpha/beta repertoire profiling, and NfL (Neurofilament Light). RECOVER biorepository serum samples will be requested for IL6, CRP, and Human Leukocyte Antigen measurement. Data from Tier 2 Neurocognitive testing will be used to examine associations between brain regions and functional networks, markers of systemic and central nervous system inflammation, and functional neurocognitive measures. Additional variables to be studied include health metrics, Long COVID symptoms, and patterns of risk associated with social drivers of health. Data will be analyzed between groups based on infection history and Long COVID status (research index) by age group.

Results: Pending.

Conclusion/Discussion: Pending.

Key Topics:

• Advanced imaging analysis to define the long term impact of COVID on organ structure/function and characterize Long COVID phenotypes
• Assay and in vitro studies to gain mechanistic insights
• Chronic immune dysfunction