International audienceThe SARS-CoV-2 B.1.1.529 (Omicron) variant, divided in five lineages (BA.1/BA.2/BA.3/BA.4/BA.5), harbors numerous spike protein mutations particularly in the receptor-binding domain (RBD). Recent studies showed that the Omicron variant resists the majority of RBD-targeting monoclonal antibodies (mAb). Sotrovimab, a pan-sarbecovirus neutralizing mAb recently authorized, seems to remain efficient to neutralize the omicron variant. However, as it targets a single epitope, the risk of developing resistance mutations is not negligible. We determined the evolution of the virus load, the development of spike mutations, and the evolution of the virus complexity in nasopharyngeal (NP) swabs from sotrovimab-treated ambulatory Om...