Differential serum neutralisation of omicron sublineages in patients receiving prophylaxis with tixagevimab–cilgavimab

[...]the use of this approach depends on the SARS-CoV-2 variant.1 Because of the rapidly changing variants, in-vitro neutralisation data using relative fold-changes in effective concentration (EC50) are frequently used to decide whether a given monoclonal antibody will be effective for a variant.2 However, these data are difficult to interpret if the serum concentration of the monoclonal antibody is not known. [...]a more clinically relevant way is to directly test variant-specific neutralisation from serum samples obtained from patients who have received the monoclonal antibody (in-vivo method). Before receiving tixagevimab–cilgavimab, 30 (40%) of 75 patients had detectable neutralisation against omicron BA.4/5, 25 (33·3%) had detectable neutralization against BQ.1.1, and 19 (25·3%) had detectable neutralisation against XBB.1.5. Since both BQ.1.1 and XBB.1.5 evade immunity conferred by vaccination, the presence of baseline neutralisation might have been driven by previous infection.6 Patients with documented previous COVID-19 infection were more likely at baseline to have BQ.1.1 neutralisation (odds ratio [OR] 4·1, 95% CI 1·3–12·7) and XBB.1.5 neutralisation (OR 5·4, 95% CI 1·7–17·4). The study was funded in part by the COVID-19 Immunity Task Force via the Public Health Agency of Canada (grant number 2122-HQ-000067 to DK).