The Omicron BQ.1.1 and XBB SARS-CoV-2 subvariants evade the monoclonal antibodies imdevimab, casirivimab, tixagevimab, cilgavimab, bebtelovimab, and S309—but not the antiviral drugs remdesivir, molnupiravir, and nirmatrelvir (Paxlovid), according to a research letter published yesterday in the New England Journal of Medicine.
A team led by University of Tokyo researchers used a live-virus neutralization assay to test the efficacy of the monoclonal antibodies and antivirals against BQ.1.1 and XBB isolated from infected patients.
Imdevimab, casirivimab, tixagevimab, cilgavimab, and S309 (precursor of sotrovimab) didn't neutralize BQ.1.1 or XBB, even at the highest concentrations tested. Bebtelovimab, which neutralizesOmicron BA.1, BA.2, BA.4, and BA.5, had no efficacy against BQ.1.1 or XBB. Neither combination of antibodies tested (imdevimab-casirivimab and tixagevimab-cilgavimab) neutralized BQ.1.1 or XBB.
Because they are no match against the newer Omicron subvariants, the only monoclonal antibody medication still authorized by the US Food and Drug Administration (FDA) to lower the risk of COVID-19 is tixagevimab-cilgavimab (Evusheld), and the FDA recently warned of its lack of efficacy in this context. The combination is reserved for people with impaired immune systems or severe adverse reactions to vaccination.
Antivirals maintained efficacy over time
BQ.1.1 and XBB were similarly susceptible to the antivirals remdesivir, molnupiravir, and nirmatrelvir as the wild-type virus. The 50% inhibitory concentration (IC50), in this case the level of antiviral needed to neutralize a subvariant, was lower by a factor of 0.6 with remdesivir and higher by factors of 1.1 and 1.2 with molnupiravir and nirmatrelvir, respectively.
For XBB, the IC50 was lower by a factor of 0.8 with remdesivir and by 0.5 with molnupiravir and higher by a factor of 1.3 with nirmatrelvir, suggesting that they are efficacious against both BQ.1.1 and XBB in vitro.
The researchers noted that, compared with older Omicron subvariants, BQ.1.1 and XBB have more mutations in the spike protein, the main target of COVID-19 vaccines and monoclonal antibodies, and thus are more likely to evade immunity. "The continued evolution of omicron variants reinforces the need for new therapeutic monoclonal antibodies for Covid-19," they wrote.