Which monoclonal antibody therapies remain effective against current Omicron sublineages and where are antivirals available locally?
Executive summary
Monoclonal antibodies that were effective early in the pandemic have lost potency against successive Omicron sublineages, and by late 2022–2024 many authorized anti‑Spike mAbs show markedly reduced neutralizing activity against newer lineages such as BQ.1.* and XBB, leaving only a shrinking set of mAbs (historically bebtelovimab and sotrovimab) with demonstrable activity against earlier Omicron descendants but uncertain utility against the most recent sublineages [1] [2] [3]. Antiviral drugs — notably nirmatrelvir/ritonavir (Paxlovid), remdesivir (Veklury) and molnupiravir — have remained broadly effective against Omicron sublineages in clinical and systematic reviews, and are the principal therapeutics health systems have relied upon when mAbs fail [4] [5] [6].
1. Monoclonal antibodies: a rapidly shrinking toolkit
Early in Omicron’s emergence regulators and hospitals pared back use of several monoclonal antibody products because they no longer neutralized the variant; Regeneron’s and Eli Lilly’s mAbs were paused or limited on the basis of reduced activity against Omicron’s spike mutations [7] [8] [9].
2. Which mAbs once worked — and the caveats
Laboratory and some clinical data showed sotrovimab and later bebtelovimab retained activity against initial Omicron sublineages (BA.1, BA.2) and were used when other mAbs failed, with bebtelovimab singled out in peer‑reviewed analyses as covering a broad set of BA.x sublineages early on [10] [2] [3] [11]. However, evolving evidence cautions that in vitro neutralization losses do not always map perfectly to clinical outcomes and that newer sublineages acquired convergent mutations that erode even these mAbs’ potency [1] [5].
3. The current scientific consensus on mAb effectiveness
By late 2022 through 2024 systematic reviews and surveillance reports concluded that monoclonal antibody therapies have experienced substantial drops in neutralizing ability across Omicron sublineages, and that some dominant lineages (for example BQ.1.*, XBB and related descendants) are notably resistant to most or all authorized anti‑Spike mAbs [4] [1] [12]. Public agencies therefore have restricted or rescinded authorizations for specific mAbs when circulating variants rendered them unlikely to benefit patients [8] [9].
4. Antivirals: the dependable backbone
Clinical studies and a network meta‑analysis found that antiviral agents such as nirmatrelvir/ritonavir (Paxlovid) and remdesivir reduce risk of hospitalization and death across Omicron sublineages, with nirmatrelvir/ritonavir showing effectiveness against BA.2/BA.4/BA.5 and sotrovimab showing benefit mainly against BA.1 in stratified analyses — evidence that antivirals remain the mainstay when mAbs fail [5] [4]. Health authorities explicitly listed Paxlovid, remdesivir and molnupiravir among therapies expected to work against Omicron when mAbs were ineffective [9] [6].
5. Where are antivirals available locally — limits of the reporting
Reporting documents hospital and state experiences procuring and distributing treatments — for example hospitals ran short of sotrovimab early in Omicron’s sweep and federal purchase agreements were used to allocate doses of new products — but the provided sources do not supply up‑to‑date, location‑specific inventories for antivirals or monoclonal antibodies at the city/clinic level; therefore definitive statements about local stock at any given site cannot be made from these documents [13] [14] [10].
6. Practical takeaway and policy context
Practically, the evidence in these reports points to relying primarily on antiviral drugs for treatment of high‑risk COVID‑19 patients because monoclonal antibodies have been outpaced by viral evolution — any use of mAbs requires current variant‑sensitivity data and regulatory authorization updates — and political disputes over allocation and policy (notably public criticism when mAbs were restricted) have intersected with clinical guidance during those shifts [4] [6] [8].
7. Uncertainties, alternative views and what to watch next
Some developers have reported candidate mAbs with broader activity in preclinical testing and governments have purchased new products for rapid deployment, but lab neutralization does not guarantee clinical protection and surveillance must continuously match therapeutics to circulating lineages; the sources note both promising leads and clear limits to mAb durability, while systematic reviews underscore antivirals’ continuing role [11] [1] [5].