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Treatment is indicated to prevent COVID-19 progression in immunocompromised patients, who may develop resistance-associated mutations due to prolonged viral shedding. During the Omicron variant surge in January–February 2022, Dutch investigators enrolled 18 SARS-CoV-2–infected patients at risk for disease progression (mean age, 61; 83% immunocompromised). All received one 500-mg infusion of sotrovimab, and nasopharyngeal swabs were collected for whole genome sequencing on the day of infusion (day 0) as well as days 7, 28, and possible additional days. The primary outcome was emergence of spike protein resistance-associated mutations.
All 18 patients were infected with Omicron (17 with BA.1, and 1 with BA.2). Within 3 to 31 days after initiating therapy, 56% of the patients developed mutations at spike protein position E340 or P337. Those who developed a resistance-associated mutation took longer to reach viral clearance than those who did not (mean, 32 vs. 20 days). Viral sequencing of Omicron in the general population revealed no strains with similar mutations.
Birnie E et al. Development of resistance-associated mutations after sotrovimab administration in high-risk individuals infected with the SARS-CoV-2 omicron variant. JAMA 2022 Aug 1; [e-pub]. (https://doi.org/10.1001/jama.2022.13854)
Comment
In this cohort of patients infected with the Omicron variant (mostly BA.1), development of sotrovimab resistance-associated mutations was fairly common, in part due to the preponderance of immune compromise among the group. Study limitations include lack of a control group and small sample size. However, these findings — and the fact that most monoclonal antibodies (including sotrovimab) lost effectiveness with the emergence of SARS-CoV-2 variants — have led most health authorities to rely on antivirals for managing COVID-19 in patients at high risk for disease progression.