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

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.

Citation

Breuer J, Drysdale M, Walker J, Han J, Aylott A, Van Dyke MK, Birch HJ, McKie E, Jordan W, Gemzoe K, Gillespie IA, Bethune C, Williams CA, Underwood J, Goodman AL, Brown M, Brown JR, Williams R, Bernal LMM, Buggiotti L, Gkrania-Klotsas E, Green C, Hunter E, Miller C, Skingsley A, Lowe DM. Monitoring the emergence of resistance with sotrovimab in immunocompromised patients with COVID-19: LUNAR study. J Infect. 2025 Jul;91(1):106510. doi: 10.1016/j.jinf.2025.106510. Epub 2025 May 19.

Type

Article