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 ![]() ![]() |
Preview |
PDF
- Accepted Post-Print Version
Available under License Creative Commons Attribution. Download (1MB) | Preview |
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 |
Actions (repository staff only)
![]() |
Edit Item |