Viral clearance and escape during therapy of COVID-19 outpatients: A prospective cohort study.

The efficacy of neutralizing SARS-CoV-2 monoclonal antibodies (mAbs) in preventing severe COVID-19 has been hindered by the diversity of viral strains and the complexity of patient populations. In this prospective cohort study, we used regression analyses to identify virological, immunological, and clinical factors associated with viral clearance and emergence of escape mutations. We included 114 mainly immunocompromised high-risk patients with mild-to-moderate COVID-19 who received mAbs or direct antivirals to prevent COVID-19 progression. Nasopharyngeal SARS-CoV-2 RNA level at day 7 was independently associated with viral load at day 0, serum neutralization at day 7, and treatment received. The emergence of mutations within Spike was observed in 21.9% of patients, all being immunocompromised treated by Sotrovimab or Tixagevimab/Cilgavimab after Omicron emergence, and was independently associated with higher viral load and serum neutralization at day 7. Our data show that suboptimal neutralizing antibodies should be avoided in immunocompromised individuals, given the risk of emergence of viral escape mutations.