This study uses total-body \[¹⁸F\]F-AraG PET/CT imaging to investigate immune activation and vascular changes in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID. Participants will undergo dynamic PET/CT imaging along with blood biomarker assessments and symptom evaluations. The study aims to characterize sites of immunological perturbation, correlate PET imaging findings with peripheral blood markers, and evaluate longitudinal changes in tissue-based immune activity in relation to symptom patterns over time. Data from this study will improve understanding of tissue-level immune dysregulation in PASC and support future clinical tools for assessing and managing this condition.
Age ≥ 18 years
Ability to understand the purposes and risks of the trial and willingness to sign an IRB-approved informed consent form.
Willingness and ability to comply with all protocol required procedures.
For participants of reproductive potential, defined as individuals who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months), or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy, willingness to use effective double barrier contraceptive methods (excluding withdrawal or timing methods) during the study and up to 1 day after the last administration of the radiotracer.
Serious comorbidities (nonmalignant disease or other conditions) that in the opinion of the investigator could compromise protocol objectives.
Any condition that alters the function of their immune system or any conditions caused by malfunction of their immune system and would interfere with imaging, including known underlying inflammatory or immune disorders, systemic malignancy, or other chronic viral infections (such as HIV, hepatitis B and hepatitis C).
Received vaccination of any type, including a SARS-CoV-2 vaccine, within 30 days of imaging
Pregnant or nursing individuals. A urine or HCG serum pregnancy test with a sensitivity of at least 25 mIU/mL will be performed at screening and on the day of PET/CT imaging at no charge to all participants of reproductive potential (see definition above).
Parallel
A.1 - [¹⁸F]F-AraG PET/CT (90-min dynamic + 4-h static)
DrugParticipants receive an intravenous injection of 5 mCi (±20%) of \[¹⁸F\]F-AraG followed by a 90-minute total-body PET/CT scan and an additional 30-minute static scan at 4 hours post-injection. Blood samples (up to 42 mL total) are collected during dynamic imaging.
A.2 - [¹⁸F]F-AraG PET/CT (60-min dynamic only)
DrugParticipants receive an intravenous injection of 5 mCi (±20%) of \[¹⁸F\]F-AraG followed by a 60-minute total-body PET/CT scan. Blood samples (up to 42 mL total) are collected during dynamic imaging.
B.1 - [¹⁸F]F-AraG PET/CT (90-min dynamic + 4-h static)
DrugParticipants receive an intravenous injection of 5 mCi (±20%) of \[¹⁸F\]F-AraG followed by a 90-minute total-body PET/CT scan and a second 30-minute scan at 4 hours. Blood samples (up to 42 mL total) are collected during dynamic imaging.
B.2 - [¹⁸F]F-AraG PET/CT (60-min dynamic only)
DrugParticipants receive 5 mCi (±20%) of \[¹⁸F\]F-AraG intravenously followed by a 60-minute total-body PET/CT scan. Blood samples (up to 42 mL total) are collected during dynamic imaging.
Quantification of [¹⁸F]F-AraG uptake kinetics in PASC and control participants
To assess immune activation in convalescent COVID-19, dynamic PET/CT scans will be analyzed to generate time-activity curves (TACs) in multiple tissues. Kinetic modeling will be applied to extract uptake parameters including SUV, SUVR, Vt, Ki, and k3. These values will be reported and statistically compared between PASC and control participants.
Correlation between [¹⁸F]F-AraG uptake parameters and blood-based markers of immune dysregulation
Spearman correlation tests and heat map clustering will be used to assess the association between PET-derived uptake measures and plasma biomarkers of inflammation and immune activation. Correlations will be examined in tissues showing significant uptake differences between study groups.
Longitudinal change in [¹⁸F]F-AraG uptake and correlation with PASC symptom scores
In a subset of participants, follow-up PET/CT imaging at 4 and 8 months will be used to assess within-subject change in kinetic uptake parameters. These changes will be compared to changes in symptom burden as measured by PHQ-15 symptom domain scores.
Feasibility of blood flow kinetic modeling using early [¹⁸F]F-AraG dynamic PET data
Early-phase TACs (\< 5 min post-injection) will be fitted using the AATH model to estimate blood flow from the vascular phase of radiotracer distribution. Identifiability of kinetic parameters associated with vascular function will be evaluated. Mean values will be compared between study groups.
Correlation between vascular imaging parameters and blood biomarkers of vascular dysfunction
Spearman correlations and heatmap analyses will be used to examine associations between PET-derived vascular parameters and plasma markers of vascular dysfunction.
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University of California, Davis
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
University of California, San Francisco
Collaborator
