The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (
Long COVID) following
SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute
SARS-CoV-2 infection using a novel
radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without
Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following
SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of
Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without
Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2
RNA and immunohistochemical studies in a subset of participants with
Long COVID symptoms. We identified cellular SARS-CoV-2
RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial
COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.