Persistent virus / viral reservoir
SARS-CoV-2 antigen or genetic material persisting in tissue reservoirs months after the acute infection.
There is growing biological evidence that viral antigen or RNA can persist in tissue reservoirs for months — circulating spike/nucleocapsid is detectable in a substantial minority of patients on ultra-sensitive (Simoa) assays. Crucially, this is biologically plausible but therapeutically unproven: the best antiviral trials for established Long COVID (Paxlovid in STOP-PASC, PAX-LC, and RECOVER-VITAL) were all null. The most plausible path forward is antigen-enriched subgroup trials, not any currently available 'antiviral protocol.' Be wary of high harm-to-evidence options like off-label high-dose herpesvirus antivirals.
How it's tested
Ultra-sensitive antigen assay (Simoa)
Single-molecule detection of circulating spike/nucleocapsid antigen months after infection — the leading research biomarker of a viral reservoir. Not yet a validated clinical test.
PCR (saliva / stool / blood)
Tests for residual viral genetic material in body fluids.
Treatment options & their evidence
Graded honestly — including treatments that failed in good trials, which is worth knowing.
Paxlovid (nirmatrelvir-ritonavir) for established LC
Failed in trialsCautionpromise 0 · 3 RCTsThree RCTs (STOP-PASC, PAX-LC, RECOVER-VITAL), including extended courses, were all null for established Long COVID. Not justified outside trials.
Caution: Strong CYP3A drug interactions via ritonavir (statins, anticoagulants, many others).