Resistance analysis in the phase III COMET-TAIL study: treatment of COVID-19 with intramuscular or intravenous sotrovimab

Aim: Sotrovimab, an engineered human monoclonal antibody, targets a conserved region of the SARS-CoV-2 spike protein. The phase III COMET-TAIL study evaluated noninferiority of intravenous versus intramuscular sotrovimab for early treatment of high-risk COVID-19 in 973 participants. Materials & methods: We investigated prevalence of variants of concern/interest (VOC/VOI) and characterized baseline, postbaseline and treatment-emergent sotrovimab epitope amino acid substitutions. Results: The Delta variant was predominant; the Alpha, Delta or Mu variants were detected in participants meeting the primary clinical endpoint for progression. Of 82 participants with sotrovimab epitope substitutions, two participants with baseline epitope substitutions met the primary endpoint for progression. Conclusion: Overall, there was no evidence that specific VOC/VOI, or postbaseline and treatment-emergent epitope substitutions, impacted clinical progression.