Characteristics and outcomes of patients with COVID-19 at high-risk of disease progression receiving sotrovimab, oral antivirals or no treatment in England

Introduction There is limited real-world evidence surrounding the effectiveness of early, mild-to-moderate COVID-19 treatments following the emergence and dominance of Omicron SARS-CoV-2 subvariants. Here, characteristics and acute clinical outcomes are described for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per NHS criteria but who were untreated. Methods Retrospective cohort study of non-hospitalised patients who received early treatment for, or were diagnosed with, COVID-19 between 1 December 2021 and 31 May 2022, using data from the Discover dataset in north-west London. Patients were included if aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or were untreated but expected to be eligible for early treatment per NHS highest-risk criteria at time of diagnosis. Outcomes were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18–64 and ≥65 years and by period of Omicron BA.1, BA.2 and BA.5 (post-hoc exploratory analysis) predominance. Results A total of 696 patients prescribed sotrovimab, 337 prescribed nirmatrelvir/ritonavir, 470 prescribed molnupiravir and 4,044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). In total, 5/696 (0.7%) patients on sotrovimab, <5/337 (0.3–1.2%) patients on nirmatrelvir/ritonavir, 10/470 (2.1%) patients on molnupiravir and 114/4,044 (2.8%) untreated patients were hospitalised with COVID-19 as the primary diagnosis. Similar results were observed across all subgroups and during Omicron subvariant periods. Conclusion Patients who received sotrovimab appeared to show evidence of multiple comorbidities that may increase risk of severe COVID-19. Low hospitalisation rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These descriptive results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics. Key points Why carry out this study? There is limited real-world evidence surrounding early, mild-to-moderate COVID-19 treatments, particularly during Omicron subvariant dominance periods, and the UK National Institute for Health and Care Excellence has recommended more is gathered. We described patient characteristics and clinical outcomes among patients treated with sotrovimab, nirmatrelvir/ritonavir, molnupiravir or who met the highest-risk eligibility criteria but were untreated. What was learned from the study? Sotrovimab was often utilised amongst more elderly and at-risk patients, such as those with advanced renal disease, than patients treated with nirmatrelvir/ritonavir or molnupiravir. We found that hospitalisation rates were low across all treated cohorts. For patients treated with sotrovimab, clinical outcomes appeared consistent when observed across the age subgroups and Omicron subvariant periods, as well as among patients with advanced renal disease.