Identifying the Long-Term Neurological Effects of COVID-19 Using 7 Tesla Multi-Modal MRI

Project Summary A growing body of evidence indicates that COVID-19 has neurological manifestations, many of which may persist post-infection. 36% to 67% of COVID-19 patients develop neurological symptoms, including anosmia, headache, and altered consciousness, and many present with severe acute neurological manifestations, including stroke. In one study, 44% of COVID-19 patients with neurological manifestations in an ICU who received an MRI had abnormal imaging findings. Given the number of individuals who have been infected with COVID-19 since early 2020, persistent neurological effects are a critical and growing public health problem. Linking the neurological effects of COVID-19 that persist in recovered patients to specific MRI-visible abnormalities remains a critical unmet need. This information will be extremely valuable in understanding how to best treat, predict, and ultimately prevent long-term neurological effects of COVID-19. 7 Tesla (7T) MRI enables us to produce images with exquisite resolution and contrast, and has revealed subtle structural and functional abnormalities in a range of neurological diseases and disorders, particularly when the abnormalities are below the threshold of detectability of conventional MRI. Highly sensitive, multi-modal neuroimaging techniques could provide new insight into the mechanisms by which SARS-CoV-2 indirectly or directly affects the brain, leading to more informed management of neurological manifestations of COVID-19 in both the acute and chronic phases. Our central hypothesis is that a retrospective analysis of COVID-19 cases with a brain MRI, followed by a prospective study using advanced 7T multimodal MRI of the brain and brainstem, will provide extensive and detailed insight into the neurological manifestations of COVID-19, allowing for improved mechanistic understanding of the chronic neurological effects of the disease and improved treatment of neurological sequelae. In this study, we will apply a 7T structural, vascular, functional, and diffusion MRI protocol to 55 patients who were previously hospitalized for COVID-19, experienced neurological symptoms during their hospitalization, and underwent clinical MRI at that time as a result of these symptoms. Scanning will be performed 6-months post-recovery. 55 age- and gender-matched healthy controls will be studied using an identical 7T protocol. The specific aims of our study are to (1) perform a retrospective analysis of 200 brain MRIs performed on COVID-19 patients with neurological symptoms and tabulate the frequencies of specific neuroimaging findings; (2) perform qualitative and quantitative analysis of 7T structural, vascular, and diffusion images in 55 recovered COVID-19 patients and compare MRI-based metrics to healthy controls; and (3) perform connectomic network analysis on functional and diffusion images to identify network differences in patients versus controls. We expect that frequencies of neurological abnormalities and quantitative metrics will differ between groups, which may highlight specific chronic neurological effects of COVID-19, and metrics of network function will differ between patients and controls, which may explain chronic effects of COVID-19.