933 – [18F]F-AraG PET Imaging Reveals Increased Gut T-Cell Activation in People With Long COVID, 2025, Henrich et al

933 – [18F]F-AraG PET Imaging Reveals Increased Gut T-Cell Activation in People With Long COVID

Timothy J. Henrich, Michael Peluso, Robert Flavell, Dylan Ryder, Kofi Asare, Emily Fehrman, Thomas Dalhuisen, Rebecca Hoh, Badri Viswanathan, Youngho Seo, Jelena Levi, Jeffrey Martin, Steven G. Deeks, Henry VanBrocklin, Emilio De Narvaez

Background
We previously demonstrated increased T cell activation across many tissue types in people months to years following SARS-CoV-2 infection compared to participants imaged prior to the COVID-19 pandemic using a novel PET imaging tracer of T cell activation ([18F]F-AraG).

The relationships between persistent whole-body T cell activation and various Long COVID (LC) clinical phenotypes, however, is not known. Thus, we performed PET imaging on 65 individuals months to years following initial COVID-19 infection and analyzed [18F]F-AraG distribution across the whole body.

Methods
Whole-body PET/CT imaging was performed ~50 minutes following [18F]F-AraG IV injection (5mCi) . Standardized uptake values (SUV) across tissue regions of interest in people with LC (n=50) at the time of imaging was compared to those who recovered rapidly after initial infection (n=15). Comparisons between LC phenotypes and SUV were performed adjusting for false discovery within tissue groups.

Results
We observed significant higher rectosigmoid wall mean SUVs in people with LC versus fully recovered (0.78 vs 0.51, P=0.019) and in people reporting cardiopulmonary (CP) symptoms (n=37; i.e., cough, shortness of breath, heart rhythm abnormalities, chest pain) vs the 28 participants that did not report CP symptoms (0.84 vs 0.57, respectively; P=0.013).

Whereas we identified a non-significant trend to higher gut tracer uptake in people reporting fatigue vs those not reporting fatigue (SUVmean 0.78 vs 0.61) there were no trends or visualized differences across tissues in other LC phenotypes (including fatigue, sleep disturbances, musculoskeletal, gastrointestinal, neurocognitive).

[18F]F-AraG uptake was similar for all other tissue regions of interest in those with LC and various LC clinical phenotypes.

Conclusions
Non-invasive PET imaging revealed increased uptake of T cell activation in colorectal tissue in those with Long COVID versus those who were fully recovered, and was specific for those reporting cardiopulmonary, but not other LC symptoms.

These findings, however, may be confounded by subclinical re-infections, vaccinations or other factors.

Nonetheless, these data support a hypothesis of ongoing GI mucosal dysfunction and potential viral persistence driving LC. Our data also suggest that the etiology of various LC clinical phenotypes is likely heterogeneous and may need to be considered as different etiologic entities.

Link (Conference on Retroviruses and Opportunistic Infections) [Abstract Only]