Imaging Immune Activation in COVID-19

Study Overview
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Brief Summary
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This is a single center, single arm exploratory imaging study involving up to two intravenous microdoses of [18F]F-AraG (the second tracer dose is optional) followed by whole-body PET-CT imaging in participants with convalescent COVID-19. Up to 20 participants will be enrolled over an accrual period of approximately 24 months. Each participant will undergo one PET-CT scan following 50 +/- 10 minutes uptake following a single bolus injection of [18F]F-AraG in order to determine the tissue distribution of tracer in pariticpants with recent SARS-CoV-2 infection. A second optional [18F]F-AraG dose and PET-CT will be offered approximately 4 months following the initial imaging time point.

Detailed Description
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This is a single center exploratory imaging study involving up to two intravenous microdoses of [18F]F-AraG (the second tracer dose is optional) followed by whole-body PET-CT imaging in participants 18 years of age and older with recent SARS-CoV-2 diagnosis and COVID-19 at least 14 days following onset of symptoms. The primary objective is to determine the anatomical distribution of [18F]F-AraG in participant with convalescent COVID-19 approximately 4 weeks and 5 months (optional, 4 months following first PET imaging visit) following onset of symptoms (N = 20). Tracer activity will also be compared with sex and age-matched uninfected historical control participants enrolled in prior studies. Up to 20 participants will be enrolled in this study who will be identified in the UCSF LIINC longitudinal COVID-19 cohort study. Each participant will undergo one PET-CT scan following 50 +/- 10 minutes uptake following a single bolus injection of [18F]F-AraG. A second optional [18F]F-AraG dose and PET-CT will be offered approximately 4 months following the initial imaging time point.

Official Title
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Imaging Immune Activation in COVID-19

Conditions
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Covid19, SARS-CoV Infection

Intervention / Treatment
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* Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Ability to read and understand written informed consent document Have a recent 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. > 14 days since onset of COVID-19 symptoms (or if no symptoms, from time of initial nucleic acid based diagnostic test). Laboratory evaluations obtained within 60 days prior to entry. Platelet count ≥75,000/mm3 ANC >1000/mm3 Aspartate aminotransferase (AST) <3 x ULN Alanine aminotransferase (ALT) <3 x ULN Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft- Gault equation Exclusion Criteria: Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator Participants who are pregnant (female participants of childbearing age will be tested prior to injection of imaging agent at entry visit/initial visit - positive test will exclude from further participation in the study) Participants who are breastfeeding Female participants of reproductive potential (defined as women 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) must have a negative urine or serum pregnancy test with a sensitivity of at least 25 mIU/mL performed within 24 hours prior to PET imaging. Females of reproductive potential will need to be on 2 forms of birth control (excluding withdrawal or timing methods). Participants who have had prior allogeneic stem cell or solid organ transplant. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <75,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <60 mL/minute, aspartate aminotransferase >3 x ULN, alanine aminotransferase >3 x ULN. Known SARS-CoV-2 shedding within 5 days of PET imaging. Previously diagnosed myelodysplasia syndrome or history of lymphoproliferative disease prior to study entry Active systemic autoimmune diseases not related to COVID-19. COVID-19 vaccine prior to the first PET imaging session. Participants may receive COVID-19 vaccination after the first PET imaging session and the optional second PET scan, with the scan being performed at least 2 weeks following the most recent vaccine dose. Prior PET scan or therapeutic radiation within 1 year of study enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single center exploratory imaging study involving up to two intravenous microdoses of [18F]F-AraG (the second tracer dose is optional) followed by whole-body PET-CT imaging in participants 18 years of age and older with recent SARS-CoV-2 diagnosis and COVID-19 at least 14 days following onset of symptoms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [18F]F-AraG<br>Radiofluorinated imaging agent, [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Trade name: VisAcT | Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)<br>* [18F]F-AraG is a radiolabeled high affinity substrate for deoxyguanosine kinase (dGK) and a low affinity substrate for deoxycytidine kinase (dCK), which are over-expressed in activated T cells.<br>* Other names: VisAcT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [18F]F-AraG uptake in participants with convalescent COVID-19 | To determine regional uptake of [18F]F-AraG in participants with convalescent COVID-19. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [18F]F-AraG uptake in participants with convalescent COVID-19 over time | To determine the anatomical distribution of [18F]F-AraG in participant with convalescent COVID-19 approximately 4 weeks and 5 months (optional) over time. | 5 months | 
| [18F]F-AraG uptake in participants with mild to severe COVID-19 symptoms | To compare maximum SUV (SUVmax) and the mean SUV (SUVmean) from regions of interest (ROI; e.g. lungs, lymph node chains,) between convalescent COVID-19 individuals with mild (N=10) to those with moderate to severe initial disease (N=10) at each imaging timepoint | 1 year | 
| [18F]F-AraG uptake in female versus male participants | To compare maximum SUV (SUVmax) and the mean SUV (SUVmean) from regions of interest (ROI; e.g. lungs, lymph node chains,) between male and female participants with convalescent COVID-19 at each imaging time point. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET-CT Imaging, [18F]F-AraG