Michael VanElzakker PhD, Instructor, Division of Neurotherapeutics, Harvard Medical School
Marco Loggia PhD, Associate Professor of Radiology, Harvard Medical School
Eva Ratai PhD, Associate Professor in Radiology, Harvard Medical School
Hannah Bues, Clinical Research Coordinator
Deena Saadi, Clinical Research Coordinator
A project to determine the extent to which glial activation (part of neuroinflammation) is contributing to ‘brain fog’ cognitive dysfunction in individuals with Long COVID. The project team is using cutting-edge dual PET-MRI neuroimaging to measure neuroinflammation (operationalized as neuroimmune glial cell activation) in Long COVID study participants. During the imaging session, study participants complete a cognitive control task while in the scanner. Data collected during the task is used to objectively measure and operationalize the ‘brain fog’ symptom, in order to test the potential contribution of microglial activation and neuroinflammation-associated metabolite concentrations to cognitive symptom severity. Blood and saliva are collected from study participants undergoing imaging, with samples analyzed for SARS-CoV-2 proteins, inflammatory markers, fibrinaloid microclot burden, and neutrophil activity. This analysis will allow the project team to determine the extent to which neuroinflammation and braig fog symptoms in individuals with Long COVID correlate with other potential drivers of the Long COVID disease process.
A common and often-debilitating core symptom of Long COVID is colloquially known as “brain fog,” which involves disruption in cognitive control or the ability to maintain focus and attention, especially in the presence of distraction. The current project is based on the understanding that cognitive control hubs in the brain are also uniquely sensitive to systemic inflammation, which several studies have reported in Long COVID. This inflammation might be due to a failure of patients with Long COVID to fully clear the SARS-CoV-2 virus (viral reservoir) or for other reasons. Immediately before scanning, blood and saliva will be collected for the measurement of inflammatory markers, microclots, and the function of live immune cells.
The project team predicts that inflammatory markers in blood will not necessarily correlate with central nervous system innate immune cell activity measured via dual PET-MRI neuroimaging (positron emission tomography-magnetic resonance imaging). These comparisons are important because simple measures of inflammation in blood are often negative in clinical testing, so the study could help clarify that the narrative “we ran tests and everything looked fine” does not necessarily account for inflammation happening in the central nervous system.