Understanding Immune Dysregulation and Vascular Dysfunction in Long COVID
Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, affects millions of individuals worldwide and is characterized by persistent, multisystem symptoms that can last months or years after the initial infection. Despite extensive research, the biological mechanisms underlying Long COVID remain poorly understood. Many hypothesized drivers—including immune dysregulation, endothelial dysfunction, viral persistence, and microvascular injury—suggest that this condition is not confined to a single organ, but involves systemic immune alterations.
Most studies to date have focused on biomarkers in peripheral blood. However, immune responses primarily occur within tissues, and direct sampling of organs such as the brain, spinal cord, heart, lungs, and gastrointestinal tract is often not feasible in living patients. There is a critical need for non-invasive tools that can assess immune activity throughout the entire body.
Our Approach
We are pioneering the use of total-body dynamic PET imaging with the [¹⁸F]F-AraG radiotracer that has selectivity for activated T-cells to simultaneously study immune activation and vascular dysfunction in Long COVID.
Using the uEXPLORER total-body PET scanner, we perform high-sensitivity dynamic imaging that captures tracer kinetics simultaneously across all organs. Rather than relying on static uptake measurements, we apply kinetic modeling to estimate physiologically meaningful parameters that reflect:
- Tracer delivery and blood flow
- Vascular permeability
- Cellular transport
- Activated T cell activity
This quantitative framework enables us to identify sites of immunological perturbation that may be masked by conventional semi-quantitative approaches.
Collaboration with UCSF LIINC
This project is conducted in close collaboration with investigators at the Long-term Impact of Infection with Novel Coronavirus (LIINC) study at UCSF, one of the in-depth phenotyped and well-characterized Long COVID cohorts in the United States.
The LIINC infrastructure provides:
- Access to a large, carefully curated cohort of individuals with diverse PASC symptom profiles
- Detailed longitudinal clinical data
- Systematic symptom phenotyping across neurological, cardiopulmonary, gastrointestinal, and constitutional domains
- Comprehensive peripheral blood biomarker analysis
By integrating total-body quantitative imaging at UC Davis with the clinical and immunologic expertise of the LIINC team at UCSF, we are able to connect tissue-level immune activation with blood biomarkers and patient-reported outcomes in a rigorously controlled framework. Importantly, we use a longitudinal design, following participants over time to determine whether changes in quantitative imaging metrics parallel changes in symptoms. This approach moves beyond group comparisons and focuses on individual disease trajectories.
This collaboration bridges advanced imaging technology with frontline clinical research in Long COVID.
Broader Impact
Although this project focuses on Long COVID, the methodological framework we are developing extends beyond a single disease. The ability to non-invasively quantify whole-body immune dynamics has implications for:
- Other post-viral syndromes
- Autoimmune disorders
- Chronic inflammatory conditions
- Therapeutic monitoring in immune-modulating treatments
Our long-term goal is to establish quantitative total-body immune imaging as a clinical research tool that enables personalized diagnostics and guides targeted interventions.
