Comment from Ruth McCrea

Anifrolumab (Anti–Type I Interferon) for Long COVID Blocking the interferon signature in an IFN-high subset | For FDA repurposing / advisory review The opportunity A type I interferon signature is a recurrent feature of Long COVID immune dysregulation, and anifrolumab is the only approved drug that selectively shuts down the type I interferon receptor. The mechanism is targeted Anifrolumab (Saphnelo) is an anti-IFNAR1 antibody that blocks all type I interferon isoforms and the downstream JAK-STAT and interferon-stimulated-gene program [1] — a precision tool rather than the broad immunosuppression of JAK inhibitors. The precedent is established Anifrolumab is FDA-approved for systemic lupus erythematosus [2], and in interferon-driven disease it normalizes the interferon signature and improves symptoms beyond JAK inhibition alone [1]. Long COVID shows persistent JAK-STAT and interferon activation [3], with the interferon gene signature serving as a ready responder biomarker. The ask A biomarker-gated trial in interferon-signature-high Long COVID — an approved, precision IFN blocker matched to a measurable immune phenotype. Sources 1. Kretzschmar G, et al. Normalized interferon signatures and clinical improvement with IFNAR1 blockade (anifrolumab) in type I interferonopathies. J Clin Immunol. 2024. 2. Anifrolumab (Saphnelo, anti-IFNAR1): FDA-approved for systemic lupus erythematosus, 2021. 3. Aid M, et al. (Barouch). Persistent JAK-STAT / interferon activation in Long COVID. Nature Immunology. 2025.