Comment from Mark Brockway
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Summary: The commenter advocates for the FDA to consider Sipavibart, a long-acting anti-spike monoclonal antibody, for repurposing to treat Long COVID. They argue that targeting antigen-positive patients using specific reservoir assays will be more effective than previous trials.
Sipavibart (Anti–Spike Monoclonal Antibody) for Long COVID
Clearing the persistent viral reservoir in antigen-positive patients | For FDA repurposing / advisory review
The opportunity
Viral antigen persistence is a leading driver of Long COVID, and we now have long-acting antibodies designed to find and neutralize that antigen — if we test them in the patients who actually carry it.
The target is real and persistent
Spike protein fragments persist in tissue for up to four years after infection, potentially driving chronic inflammation and autoimmunity [1], and roughly 43% of Long COVID patients have detectable circulating spike or nucleocapsid antigen up to 14 months out, correlating with symptoms [2].
The therapy and the program exist
Sipavibart is a long-acting, broadly neutralizing anti–spike monoclonal antibody (AstraZeneca). The Invivyd-led SPEAR Study Group, with leading viral-persistence investigators, is structuring anti-spike mAb trials for Long COVID [3], a sipavibart Long COVID trial is enrolling at Nova Southeastern (Klimas) [4], and a parallel UCSF program (Peluso) tests the anti-spike mAb AER002 against the reservoir [5].
Why it succeeds where earlier trials did not
Early short-course mAb attempts enrolled unselected patients. Gating enrollment to antigen-positive patients identified by the now-available reservoir assays targets the therapy at exactly the people whose disease it can address.
The ask
An antigen-biomarker-gated trial of a long-acting anti–spike mAb, with access expanded beyond a single site. The biology, the assay, and the antibody all now exist.
Sources
1. SARS-CoV-2 spike protein persistence in tissue up to 4 years post-infection. 2025.
2. Detectable SARS-CoV-2 spike/nucleocapsid antigen in ~43% of Long COVID patients up to 14 months; JCI Insight complement review (Swank et al. data). 2025.
3. Invivyd / SPEAR (Spike Protein Elimination and Recovery) Study Group, anti-spike mAb Long COVID trials. July 2025.
4. Sipavibart Long COVID trial, INIM / Nova Southeastern (Klimas); AstraZeneca.
5. Anti-SARS-CoV-2 mAb AER002 for Long COVID, UCSF (Peluso), NCT05877508.