Whole-body PET imaging reveals tissue-based immune activation and SARS-CoV-2 persistence in the post-acute phase of COVID-19

The study titled “Whole-body PET imaging reveals tissue-based immune activation and SARS-CoV-2 persistence in the post-acute phase of COVID-19” investigated the underlying mechanisms of Long COVID and post-acute medical issues following SARS-CoV-2 infection. Using whole-body positron emission tomography (PET) imaging on 24 participants, it employed a novel radiopharmaceutical agent, [18F]F-AraG, to quantitatively visualize activated T lymphocytes in various anatomical regions.

Key Findings:

  1. Elevated T Cell Activation: Increased T cell activation was observed in the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall compared to pre-pandemic controls.
  2. Persistence of Activation: Elevated tracer uptake, indicating T cell activation, persisted in participants up to 2.5 years following infection, regardless of Long COVID symptoms.
  3. Link with Long COVID Symptoms: Participants with Long COVID symptoms showed higher tracer uptake in specific tissues, such as the spinal cord and gut wall, suggesting a potential association with prolonged symptoms.
  4. Lung Tissue Activation: Increased tracer uptake in lung tissue correlated with persistent pulmonary symptoms.
  5. SARS-CoV-2 RNA Detection: Cellular SARS-CoV-2 RNA was identified in colorectal tissue, implying that tissue viral persistence could be linked to long-term immunological disturbances.
  6. Demographics and Clinical Factors: Participants included individuals both with and without complete recovery from COVID-19, with a median age of 39.5 years. Common symptoms included fatigue and neurocognitive complaints.

Methodology:

  • The study enrolled 24 participants from the UCSF-based LIINC cohort, imaged at varying intervals post-COVID-19 infection.
  • Chest CTs and [18F]F-AraG PET/CT imaging were used to assess T cell activation and cycling.
  • The study also measured SARS-CoV-2 nucleocapsid IgG levels and conducted high-dimensional flow cytometric evaluation of blood and gut-derived mononuclear cells.

Limitations:

  • Small sample size limited the power of certain tissue and immune correlative studies.
  • Rapid evolution of the pandemic and changes in the protocol over time.
  • Reliance on pre-pandemic controls with different imaging protocols.

Conclusion: The study provides evidence for ongoing immune responses in tissues, potentially contributing to inflammation observed in peripheral blood. It suggests that SARS-CoV-2 infection could lead to a new immunologic steady state, contributing to Long COVID and post-acute sequelae. However, further research is needed to fully understand these relationships and the long-term consequences of SARS-CoV-2 infection​​​​.

Read More; https://www.medrxiv.org/content/10.1101/2023.07.27.23293177v1.full.pdf

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