Why Long COVID Won't Resolve: A Mechanistic Reading of Viral Persistence, Mitochondrial Dysfunction, and the Gut–Brain Axis the Standard Model Is Missing — Part 1: What Three Years of Long COVID Research Actually Shows

A careful reading of the 2022–2026 literature reveals approximately nine distinguishable mechanistic findings that are now reasonably well-supported, replicated across cohorts, and connected to specific symptom domains. I will summarize each briefly, with the relevant primary literature. The integration follows in Part 2. Finding One: Persistent Viral Antigen in Gut Tissue SARS-CoV-2 RNA, spike protein, and viral nucleocapsid antigen have been documented in intestinal tissue and stool months to years after acute infection in subsets of long COVID patients. The intestinal epithelium expresses ACE2 at high density, particularly in the small intestine, and is one of the documented anatomical reservoirs where viral antigen persists when respiratory clearance has occurred. Studies have demonstrated viral RNA in colonic biopsies four to seven months after acute infection, and circulating spike antigen detection in plasma in some long COVID cohorts at twelve months and beyond. The persistence is not necessarily replicative infection. It is more often persistent antigen — viral RNA fragments, isolated proteins, or non-productive viral remnants — that provides a continuous low-grade signal to the gut immune system. The continuous signaling drives the downstream inflammatory cascade rather than being curatively addressed by antiviral courses, which are designed to suppress replication ra