Full Citation:: Peluso MJ, et al. Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection. Science Translational Medicine. 2024;16(754):eadk3295. (Peluso et al. 2024) DOI:: 10.1126/scitranslmed.adk3295 Study Design:: Total-body PET-CT imaging \(+\) rectosigmoid biopsies Key Findings::
- SARS-CoV-2 spike-encoding RNA (ssRNA and dsRNA) detected in gut lamina propria up to 676 days (nearly 2 years) after initial infection
- Double-stranded RNA constitutively activates innate immune sensors (RIG-I, MDA5), generating persistent interferon signature without active replication
- Viral RNA persistence associated with ongoing T cell activation in gut-associated lymphoid tissue
- Total-body PET showed widespread lymphoid tissue involvementRelevance:: Landmark mechanistic evidence for the viral reservoir model of Long COVID and post-COVID ME/CFS. The dsRNA-innate sensor activation mechanism elegantly explains perpetual immune activation without requiring ongoing viral replication. Also has diagnostic and therapeutic implications: PET imaging as biomarker; extended antiviral courses as treatment. Certainty Assessment::
- *Quality:* High (Science Translational Medicine; direct tissue evidence)
- *Sample:* Small biopsy cohort ($n=5$ rectosigmoid biopsies) within larger PET study
- *Replication:* Consistent with multiple independent viral persistence studies
- *Certainty:* 0.70
- *Limitation:* Small biopsy $n$; causal relationship between gut reservoir and systemic symptoms not yet directly tested