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

Abstract

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.

Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: a retrospective cohort study

“…Those which have studied similar cohorts, including one peer-reviewed and one pre-print study exploring the UK’s targeted deployment, also reported lower rates of hospital admission and death amongst those receiving treatment. 26,27 Whilst in contrast to the findings of our secondary analysis, Zheny et al reported sotrovimab treatment was associated with a reduced risk of death or hospitalisation within 28 days of a positive COVID-19 test when compared with molnupiravir, neither that study nor the pre-print study conducted by Patel et al, were designed to compare the effectiveness of treatment to no treatment, in the high-risk cohort.…”

Characteristics and Outcomes of COVID-19 Patients Presumed to be Treated with Sotrovimab in NHS Hospitals in England

“…Nonetheless, our results are consistent with those from a recent study, conducted between 16 th December 2021 and 10 th February 2022 using the OpenSAFELY-TPP platform, which reported that 0.96% of patients confirmed to have been treated with sotrovimab had a COVID-19-attributable hospitalisation or death within 28 days of treatment [14]; in our study, 1.0% of patients who were assumed to have been treated with sotrovimab experienced a COVID-19-attributable hospitalisation in the 28-day post-treatment acute period. The results are also similar to those of another recently completed analysis that used data from the Discover database in North-West London, which reported 0.7% of people confirmed to have been treated with sotrovimab experiencing a COVID-19-attributable hospitalisation during the 28 days following treatment (study period was 1 st December 2021 – 31 st May 2022 with subvariants predominance as follows: Omicron BA.1 from 1 st December 2021 – 28 th February 2022 and Omicron BA.2 from 1 st March 2022 – 31 st May 2022) [15]. Similarly, our findings of low rates of COVID-19-attributable deaths and hospitalisations in patients with advanced kidney disease are consistent with a those from a recent study in non-hospitalised patients with COVID-19 on kidney replacement therapy; treatment with sotrovimab resulted in a substantially lower risk of severe COVID-19 outcomes compared with molnupiravir during periods of Omicron BA.1 through to BA.5 subvariant dominance [16].…”

Effectiveness of Nirmatrelvir-Ritonavir for the treatment of patients with mild to moderate COVID-19 and at high risk of hospitalization: Systematic review and meta-analyses of observational studies

“…The following are the results of the meta-analyses conducted by the evaluated outcome. Three studies reported subgroup data by vaccination status (11,14,18) and four other studies reported data by age group (14,18,19,24). In the analysis by vaccination status, nirmatrelvir-ritonavir reduced the risk of mortality both in the unvaccinated group (OR=0.41; 95% CI: 0.29-0.58) and in the vaccinated group (OR=0.31; 95% CI: 0.14-0.68), with no significant difference between the groups (Fig 3A).…”

“…The sixteen studies finally considered were conducted in 5 countries (Canada, China, United States, Israel, and United Kingdom). Of these, as of the last update of the search, 12 studies were published (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and 4 were unpublished studies (preprint) (23)(24)(25)(26). All studies were retrospective cohorts of data obtained from electronic records of hospitals and other healthcare centers, collected from January 2021 to October 2022.…”

“…Regarding the initiation of treatment with nirmatrelvir-ritonavir, 8 studies were strict with the initiation of treatment within the fifth day of symptom onset or positive COVID-19 test (11,12,(17)(18)(19)(20)24,25). In the other 6 studies, there was greater flexibility, as patients started treatment with nirmatrelvir-ritonavir within 10 days of symptom onset or positive test (15,16,(21)(22)(23)26).…”