Comment from Gillian McCrea

Ensitrelvir (Xocova) for Long COVID A next-generation oral antiviral for viral persistence | For FDA repurposing / advisory review The opportunity If residual virus drives Long COVID, patients need an antiviral that can be given long enough, and reach deep enough, to clear it. Ensitrelvir is built for exactly that. Why ensitrelvir, not Paxlovid Short 15-day courses of nirmatrelvir/ritonavir (Paxlovid) did not improve Long COVID in two randomized trials — a problem of duration and patient selection, not the antiviral premise [1]. Ensitrelvir is an oral 3CL protease inhibitor that is once-daily, needs no ritonavir boost, and has far fewer drug interactions — the pharmacology that makes extended-duration dosing feasible. It is already approved Ensitrelvir (Xocova) was FDA-approved in 2026 for COVID-19 [2]. The molecule, manufacturing, and safety data exist; it is simply not available to Long COVID patients. The ask An extended-course trial of ensitrelvir gated to antigen- or RNA-positive Long COVID patients — the design the earlier antiviral trials lacked. Approved drug, defined target population, ready to test. Sources 1. STOP-PASC (JAMA Intern Med, 2024) and PAX LC (Lancet Infect Dis, 2025): 15-day nirmatrelvir/ritonavir showed no benefit in Long COVID; futility-stopped, single-site, unselected. 2. Ensitrelvir (Xocova): FDA approval for COVID-19, 2026 (The Sick Times, June 2026). 3. Viral persistence / reservoir hypothesis supporting sustained antiviral therapy in a defined subset.