Monitoring the emergence of resistance with sotrovimab in immunocompromised patients with COVID-19: LUNAR study

Abstract

Objectives

To assess outcomes in sotrovimab-treated immunocompromised patients in the United Kingdom.

Methods

Multicenter, prospective, observational, descriptive study in immunocompromised, non-hospitalized adults infected with SARS-CoV-2 who received intravenous sotrovimab 500 mg as standard-of-care (July 1, 2022–June 30, 2023; Omicron predominance). Virology analyses included determination of SARS-CoV-2 viral load, spike sequencing, and determination of amino-acid substitutions in the spike protein and sotrovimab epitope.

Results

The proportion of participants (N = 217) with undetectable SARS-CoV-2 RNA was 25.1% at day 7, 65.8% at day 14%, and 83.5% at day 28. Of 156 participants with paired sequences, 101 (64.7%) and 47 (30.1%) had treatment-emergent substitutions at >50% allelic frequency in the spike protein and sotrovimab epitope, respectively, at any post-baseline timepoint. Ten treatment-emergent substitutions (at positions 337, 340, and 356) were identified in the epitope at >50% allelic frequency. Five of 18 (27.8%) participants with, versus 22/30 (73.3%) of those without, treatment-emergent epitope substitutions at day 14 achieved undetectable SARS-CoV-2 RNA levels at day 28.

Conclusions

In this immunocompromised population infected with SARS-CoV-2 who received early treatment with sotrovimab, most participants (83.5%) experienced substantial viral load reductions by day 28. Treatment-emergent substitutions occurred in the sotrovimab epitope, including substitutions known to reduce susceptibility in vitro. Several treatment-emergent substitutions were associated with viral persistence.