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.

Introduction:There is uncertainty regarding howin vitroantibody neutralisation activity translates to the clinical efficacy of sotrovimab against severe acute respiratory syndrome coronavirus 2, although real-world evidence has demonstrated continued effectiveness during both BA.2 and BA.5 predominance. We previously reported descriptive results from the Discover dataset for patients treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per National Health Service (NHS) criteria but who were untreated. This study sought to assess the effectiveness of sotrovimab compared with no early coronavirus disease 2019 (COVID-19) treatment in highest-risk patients with COVID-19.Methods:Retrospective cohort study using the Discover dataset in North West London. Patients had to be non-hospitalised at index, aged ≥12 years old and meet ≥1 of the NHS highest-risk criteria for receiving early COVID-19 treatment with sotrovimab. The primary objective was to assess the risk of COVID-19-related hospitalisation and/or COVID-19-related death within 28 days of the observed/imputed treatment date between patients treated with sotrovimab and highest-risk patients who received no early COVID-19 treatment. We also performed subgroup analyses for patients aged <65 and ≥65 years, patients with renal dysfunction, and by Omicron subvariant prevalence period (BA.1/2 emergence: 1 December 2021–12 February 2022 [period 1]; BA.2 reaching and at its peak: 13 February–31 May 2022 [period 2]; BA.2 falling and BA.4/5 emergence: 1 June–31 July 2022 [period 3]). Inverse probability of treatment weighting based on propensity scores was used to adjust for measured known and likely confounders between the cohorts. Cox proportional hazards models with stabilised weights were performed to assess hazard ratios (HRs).Results:A total of 599 highest-risk patients treated with sotrovimab and 5,191 untreated highest-risk patients were included. Compared with untreated patients, sotrovimab treatment reduced the risk of COVID-19 hospitalisation or death by 50% (HR=0.50; 95% confidence interval [CI] 0.24, 1.06); however, statistical significance was not reached (p=0.07). In addition, sotrovimab reduced the risk of COVID-19 hospitalisation by 57% (HR=0.43; 95% CI 0.18, 1.00) compared with the untreated group, although also not statistically significant (p=0.051). Among patients aged ≥65 years and patients with renal disease, sotrovimab treatment was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR=0.11; 95% CI 0.02, 0.82; p=0.03) and 82% (HR=0.18; 95% CI 0.05, 0.62; p=0.007), respectively. In period 1, sotrovimab treatment was associated with a 75% lower risk of COVID-19 hospitalisation or death compared with the untreated group (HR=0.25; 95% CI 0.07, 0.89; p=0.032). In periods 2 and 3, HRs of COVID-19 hospitalisation or death were 0.53 (95% CI 0.14, 2.00; p=0.35) and 0.78 (95% CI 0.23, 2.69; p=0.69), respectively, for the sotrovimab versus untreated groups, but differences were not statistically significant.Conclusions:Sotrovimab treatment was associated with a significant reduction in risk of COVID-19 hospitalisation in patients aged ≥65 years and those with renal disease compared with the untreated cohort. For the overall cohort, the risk of hospitalisation following sotrovimab treatment was also lower compared with the untreated group; however, this did not achieve statistical significance (p=0.051). The risk of hospitalisation and/or death was lower for the sotrovimab-treated cohort across all time periods but did not reach significance for periods 2 and 3.