Whole-body [18F]F-AraG PET/CT to map immune activity in Long COVID

Multiparametric Total-Body [18F]F-AraG PET/CT Imaging in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

This research will try a total-body [18F]F-AraG PET/CT scan plus blood tests to see if they can detect ongoing immune activity in adults with Long COVID compared with recovered controls.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, Davis (other)
• Locations: 2 sites (Sacramento, California and 1 other locations)
• Trial ID: NCT07076862 on ClinicalTrials.gov

What this trial studies

This is a prospective, non-randomized, open-label imaging study using the investigational radiotracer [18F]F-AraG to map activated T cells across the body in people with post-acute sequelae of SARS-CoV-2 infection (PASC) and in recovered controls. Participants undergo dynamic total-body PET/CT imaging, peripheral blood draws for proteomics and immunophenotyping, and symptom questionnaires through the UCSF LIINC cohort. A total of 51 people will be enrolled (34 PASC and 17 controls), and 17 PASC participants will have follow-up scans at 4 and 8 months to measure longitudinal changes. Imaging findings will be correlated with blood biomarkers and symptom patterns to identify tissue-specific immune signatures linked to clinical features.

Who should consider this trial

Good fit: Adults aged 18 or older with a prior laboratory-confirmed SARS-CoV-2 infection and ongoing PASC symptoms who can undergo PET/CT scanning and blood draws are ideal candidates.

Not a fit: People without documented prior SARS-CoV-2 infection, those who are pregnant or breastfeeding, or those unable to tolerate PET/CT imaging are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could provide imaging and blood-based tools to identify tissue-level immune changes in Long COVID, helping with diagnosis and monitoring in the future.

How similar studies have performed: Immune-targeted PET tracers have shown promise in preclinical and early human work for imaging T cell activation, but applying [18F]F-AraG imaging specifically to Long COVID is a relatively new approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Ability to understand the purposes and risks of the trial and willingness to sign an IRB-approved informed consent form.
3. Willingness and ability to comply with all protocol required procedures.
4. 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.
5. Previous diagnosis of SARS-CoV-2 infection as defined by a prior positive SARS-CoV-2 nucleic acid-based diagnostic test performed in a clinical laboratory on one or more nasopharyngeal or respiratory secretion samples or from an FDA-approved rapid antigen test at home. Documentation of the positive test will be requested but not required; if not available the participant will be asked to attest to the presence of a positive test.
6. Onset of COVID-19 symptoms (or if no symptoms, time of initial nucleic acid or antigen-based diagnostic test) at least 3 months prior to the baseline study visit.
7. Ability to travel to our research sites in San Francisco and Sacramento.
8. Laboratory evaluations obtained within 60 days prior to entry:

   1. Hemoglobin ≥ 8g/dL
   2. Platelet count ≥ 75,000 cells/mm3
   3. Absolute neutrophil count (ANC) \> 1000 cells/mm3
   4. Aspartate aminotransferase (AST) \< 3 × ULN units/L
   5. Alanine aminotransferase (ALT) \< 3 × ULN units/L
   6. Calculated creatinine clearance (CrCl) ≥ 60mL/min as estimated by the Cockcroft-Gault equation:

   For men, (140 - age in years) × (body weight in kg) ÷ (serum creatinine in mg/dL × 72) = CrCl (mL/min)\*

   \*For women, multiply the result by 0.85 = CrCl (mL/min)
9. For PASC participants only: Reporting at least 2 unexplained symptoms, with at least 1 symptom in the fatigue domain and at least 1 symptom in either cardiopulmonary or neurocognitive domains, that last for at least 2 months and cannot be explained by an alternative diagnosis. Symptoms may be new onset after initial COVID-19 recovery or persist from the initial acute phase and may fluctuate or relapse over time. (According to World Health Organization definition of PASC http://www.WHO.int )
10. For control participants only: Individuals who have made full clinical recovery within 4-12 weeks of acute COVID-19 infection with no newly developed symptoms or changes in health after recovery.

Exclusion Criteria:

1. Serious comorbidities (nonmalignant disease or other conditions) that in the opinion of the investigator could compromise protocol objectives.
2. 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).
3. Received vaccination of any type, including a SARS-CoV-2 vaccine, within 30 days of imaging
4. 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).
5. Participants who have had prior allogeneic stem cell or solid organ transplant.
6. Previously diagnosed myelodysplasia syndrome or history of lymphoproliferative disease prior to study entry.
7. Active systemic autoimmune diseases not related to COVID-19.
8. Self-reported history of dysphoria or anxiety in closed spaces (i.e., uncontrolled claustrophobia).
9. Concurrent or prior enrollment in a separate research study involving a PET scan performed within the last 12 months for research purposes only.
10. Body weight is more than 240 kg (529 pounds)
11. Prisoners
12. Life expectancy \< 24 months
13. Recent use of medication including guanosine or cysteine analogs.
14. Any other criteria which would make the participant unsuitable for enrollment to this study, as determined by the Principal Investigator.

Where this trial is running

Sacramento, California and 1 other locations

• UC Davis EXPLORER Molecular Imaging Center — Sacramento, California, United States (RECRUITING)
• University of California San Francisco — San Francisco, California, United States (RECRUITING)

Study contacts

• Principal investigator: Negar Omidvari, PhD — University of California, Davis
• Study coordinator: Clinical Research Team

Conditions: PASC Post Acute Sequelae of COVID-19