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). Effects of COVID-19 on the CNS in the acute phase were documented clinically, by magnetic resonance imaging (MRI) and spectroscopy (MRS), by plasma biomarkers and at autopsy, with neurological symptoms manifesting in 1/3 to 2/3 of hospitalized, severe cases. After the acute phase, approximately 10% of patients experience prolonged illness, during which neurological symptoms (headaches, cognitive blunting, and fatigue) are among the top 10 symptoms reported by COVID-19 survivors. The underlying biology of these prolonged symptoms is unknown; therefore, prospective studies to systematically investigate the pathophysiology of such sequelae are urgently needed. Based on the clinical presentation of COVID-19, reports of COVID-related symptoms in the months following the infection, including reports of Parkinsonism and other delayed neurological and neurocognitive complications ranging from mild-to-severe, and known peripheral triggers of cerebral pathology, neuroinflammation (Aim 1), neurodegeneration (Aim 2) and cerebrovascular disease (CVD) (Aim 3) are expected to be important components of long-term CNS pathophysiology. The COVID BRain Advanced Imaging Network (COVID-BRAIN) was formed as a Consortium of six institutions to systematically and prospectively elucidate the long-term CNS pathophysiology of COVID-19 using highly sensitive, harmonized, advanced MRI/MRS technology at 3 tesla in conjunction with standardized neurological and neuropsychological evaluation and inflammatory blood biomarkers. Five sites that currently 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) will collect longitudinal multi-modal MRI (T1, FLAIR, diffusion MRI, susceptibility-weighted MRI, single- and multi-voxel MRS and pseudo-continuous arterial spin labeling), clinical, neurocognitive and blood biomarker data from laboratory confirmed post-COVID cases with neurological symptoms (N=200) and matched controls (N=100). The Laboratory of Neuro Imaging (LONI) at the University of Southern California will serve as the data management site. Group differences and change over time in MR markers indicative of neuroinflammation, neurodegeneration, hypoxia/ischemia and CVD and their associations with specific neurological symptoms, cognitive function, and inflammatory blood biomarkers will be investigated. The mechanistic insights provided by this study will inform the care and treatment of patients that are expected to suffer long-term consequences of the pandemic for the years to come.