David Izquierdo-Garcia PhD, Assistant Professor of Radiology, Harvard Medical School/MGH
Michael VanElzakker PhD, Instructor, Division of Neurotherapeutics, Harvard Med. School/MGH
Leo Ginns, MD, Associate Professor of Medicine, Harvard Med. School/Mass. General Hospital
George Alba, MD, Instructor, Pulmonology & Critical Care, Harvard Medical School/MGH
Sydney Montesi, MD, Assistant Professor of Medicine, Harvard Medical School/MGH
The project is the first in the world to use advanced positron emission tomography (PET) imaging to test the hypothesis that Long COVID symptoms could result in part from fibrin accumulation in body sites such as the lung, heart, and brain. The team will determine if fibrin accumulation may be accompanied by endothelial (blood vessel) permeability and the formation of fibrinaloid microclots in circulating blood. Specifically, the team will use a novel fibrin-binding PET radiotracer ([64Cu]-FBP8) to image fibrin deposition throughout the bodies & brains of Long COVID patients and matched COVID-recovered controls. They will also employ dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure endothelial permeability in study participants. Imaging will be accompanied by analyses of patient blood including 1) fluorescence microscopy to characterize fibrinaloid microclot burden 2) neutrophil functional assays 3) peripheral blood immunoassays to measure cardiovascular health parameters. Data obtained via these different analyses will be compared with clinically-collected longitudinal heart and lung function data also obtained from study participants in order to determine if fibrin deposition, endothelial permeability, or other metrics measured by the whole-body PET-MR imaging and blood tests predict specific Long COVID symptoms.
Additional project information:
Early Long COVID research indicates that fibrin deposition or endothelial dysfunction may contribute to symptoms in patients with the condition. For example, fibrin/amyloid microclots resistant to breakdown (fibrinolysis) have been identified in Long COVID blood. These microclots may block blood flow and oxygen delivery to body tissues and blood vessels. The SARS-CoV-2 spike protein has even been shown to bind to fibrinogen and induce structurally abnormal blood clots with heightened proinflammatory activity. It follows that further research on fibrin deposition and endothelial dysfunction is a major priority for the Long COVID community. However, studies of blood alone cannot test for fibrin deposition or endothelial dysfunction in tissue body sites such as the lung, heart, and brain. The project team will therefore use advanced PET imaging techniques to measure deep tissue fibrin deposition and endothelial permeability in their Long COVID study participants. Findings from the study could help determine how antifibrinolytic supplements or anticoagulants might best be positioned into Long COVID clinical trials.