Understanding the long term impact of COVID-19 on the brain through advanced MR imaging and spectroscopy

PROJECT SUMMARY/ABSTRACT Since the World Health Organization declared COVID-19 a pandemic in March 2020, increasing evidence has shown that the disease affects multiple organs, including the central nervous system (CNS). The COVID BRain Advanced Imaging Network (COVID-BRAIN) was formed to elucidate the long-term CNS pathophysiology of COVID-19 systematically and prospectively. We use highly sensitive, harmonized, advanced MR technology at 3 tesla to interrogate neuroinflammation, neurodegeneration and cerebrovascular disease in individuals with persistent neurological sequalae following SARS-CoV-2 infection. Five sites that also partner in other multi-site neuroimaging initiatives (University of Minnesota, Mayo Clinic Rochester, Harvard University/Massachusetts General Hospital, Johns Hopkins University, Houston Methodist Research Institute) collect longitudinal multi-modal MRI (T1, FLAIR, diffusion MRI, susceptibility-weighted MRI, single- and multi-voxel MR spectroscopy and pseudo-continuous arterial spin labeling), clinical, neurocognitive and inflammatory blood biomarker data from laboratory confirmed post-COVID cases with neurological symptoms and matched controls. The pathophysiologic components of CNS injury associated with COVID-19 can potentially lead to increased risk for Alzheimer's disease and its related dementias (AD/ADRD) as emphasized in the 2022 ADRD Summit recommendations. Therefore, in Aim 1, we will assess AD/ADRD risk in patients with long-COVID using blood-based biomarkers (Abeta 1-40, Abeta 1-42, pTau181, NfL and GFAP) and determine whether APOE ε4 status, age, sex, race, ethnicity, and social determinants of health modify this risk. In Aim 2, we will investigate the associations of these blood-based biomarkers with MRI/MRS markers of neuroimflammation, neurodegeneration and cerebrovascular disease in patients with long-COVID and whether APOE ε4 status, age, sex, race, ethnicity, and social determinants of health modify these associations. The insights provided by this study will be critical for developing disease-modifying therapies targeting the underlying pathologic mechanisms associated with the long-term CNS consequences of COVID-19, including increased risk for AD/ADRD.