Breuer, Judith, Drysdale, Myriam, Walker, Jill, Han, Jennifer, Aylott, Alicia, Van Dyke, Melissa K., Birch, Helen J., McKie, Elizabeth, Jordan, William, Gemzoe, Kim, Gillespie, Iain A., Bethune, Claire, Williams, Charlotte A., Underwood, Jonathan  ORCID: https://orcid.org/0000-0001-6963-2821, Goodman, Anna L., Brown, Michael, Brown, Julianne R, Williams, Rachel, Bernal, Luz Marina Martin, Buggiotti, Laura, Gkrania-Klotsas, Effrossyni, Green, Clara, Hunter, Ewan, Miller, Charles, Skingsley, Andrew and Lowe, David M.
2025.
Monitoring the emergence of resistance with sotrovimab in immunocompromised patients with COVID-19: LUNAR study.
Journal of Infection
, 106510.
10.1016/j.jinf.2025.106510
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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.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Medicine |
| Publisher: | Elsevier |
| ISSN: | 0163-4453 |
| Funders: | GSK |
| Date of First Compliant Deposit: | 20 May 2025 |
| Date of Acceptance: | 11 May 2025 |
| Last Modified: | 21 May 2025 08:48 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/178386 |
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