Comparison of the risk of hospitalisation among BA.1 and BA.2 COVID-19 cases treated with Sotrovimab in the community in England

Harman, Katie; Nash, Sophie; Webster, Harriet; Groves, Natalie; Hardstaff, Jo; Bridgen, Jessica R E; Blomquist, Paula; Hope, Russell; Ashano, Efejiro; Rokadiya, Sakib; Hopkins, Susan; Brown, Colin S; Chand, Meera; Dabrera, Gavin; Thelwall, Simon

doi:10.1101/2022.10.21.22281171

Cited by 20 publications

(62 citation statements)

References 6 publications

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“…We recently showed that sotrovimab (S309) retained in vitro effector functions against BA.2 and conferred Fc-dependent protection in the lungs of mice infected with BA.2 67 . This preclinical finding is supported by the accumulation of real-world evidence suggesting that adverse clinical outcomes, such as hospitalization and mortality, remained consistently low during the BA.2 wave in patients treated with sotrovimab [68][69][70][71][72] . Here, we show that sotrovimab retained in vitro effector functions against all Omicron variants at levels comparable to those observed with Wu.…”

Section: Discussionmentioning

confidence: 70%

Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants

Addetia

Piccoli

Case³

et al. 2023

Preprint

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Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots. Their impact on viral infection, transmission, and efficacy of vaccines and therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. and XBB.1 variants bind ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1 and XBB.1 RBDs bound to human ACE2 and S309 Fab (sotrovimab parent) explain the altered ACE2 recognition and preserved antibody binding through conformational selection. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1, the variant displaying the greatest loss of neutralization. Moreover, in several donors vaccine-elicited plasma antibodies cross-react with and trigger effector functions against Omicron variants despite reduced neutralizing activity. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring persistent immune imprinting. Our findings suggest that this previously overlooked class of cross-reactive antibodies, exemplified by S309, may contribute to protection against disease caused by emerging variants through elicitation of effector functions.

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Section: Discussionmentioning

confidence: 70%

Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants

Addetia

Piccoli

Case³

et al. 2023

Preprint

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“…31 Moreover, sotrovimab was found to offer a similar level of protection against disease progression in patients with COVID-19 infected with the Omicron BA.1 and BA.2 subvariants. 32 Similarly, in an observational study in the US, treatment with sotrovimab was associated with a reduced risk of all-cause hospitalisation and mortality during the predominance of early Omicron variants. 33 This study has several limitations that should be considered.…”

Section: Discussionmentioning

confidence: 95%

“…30 The results of this study compliment other recent real-word studies on early treatments for COVID-19 in the UK. [31][32][33] For example, the findings of a recent publication on the comparative effectiveness of sotrovimab versus molnupiravir in England, conducted using the OpenSAFELY platform, showed that sotrovimab treatment was associated with a significant reduction in risk of severe COVID-19 outcomes in comparison to treatment with molnupiravir during BA.1 (primary analysis) and BA.2 (exploratory analysis) predominance. 31 Moreover, sotrovimab was found to offer a similar level of protection against disease progression in patients with COVID-19 infected with the Omicron BA.1 and BA.2 subvariants.…”

Section: Discussionmentioning

confidence: 99%

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

Yarwood

Levick²,

Gibbons

et al. 2022

Preprint

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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.

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“…Recent observational studies conducted in Europe suggest continued clinical effectiveness of sotrovimab through the Omicron BA.2 surge. In a study of >8000 patients in England, there were no differences in the risk of hospitalization for patients with mild to moderate COVID-19 treated with sotrovimab who were infected with the Omicron BA.1 or BA.2 SARS-CoV-2 variants [22].…”

Section: Introductionmentioning

confidence: 98%

“…These were progression of COVID-19 through Day 29 as defined by hospitalization >24 hours for acute management of illness due to any cause or death; or visit to a hospital emergency room for management of illness or hospitalization for acute management of illness for any duration and for any cause or death; development of severe COVID-19 requiring respiratory support including oxygen at Days 8, 15, 22 and 29; and the incidence of participants requiring intensive care unit (ICU) stay or mechanical ventilation through Day 29. Viral load in nasal secretions was assessed using quantitative RT-PCR and evaluated as the change from baseline in viral load atDays 3,5,8,11,15,22,and 29; undetectable SARS-CoV-2 in nasal secretions atDays 3,5,8,11,15,22,and 29; and the proportion of participants with a persistently high SARS-CoV-2 viral load (≥4.1 log 10 copies/mL) at Day 8.…”

mentioning

confidence: 99%

Safety, Virology, Pharmacokinetics, and Clinical Experience of High-dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-label Clinical Trial

Moya

Temech

Parra

et al. 2023

Preprint

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Background: 500 mg intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression. Methods: This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.5, BA.2.12.1, and BA.4 were the predominant circulating variants in the United States. The primary endpoint was occurrence of adverse events (AEs), serious AEs (SAEs), AEs of special interest, and COVID-19 disease-related events (DREs) through Day 8. Safety, pharmacokinetics, viral load, and hospitalization >24 hours for acute management of illness or death through Day 29 were assessed. Results: All participants (n=81) were Hispanic, 58% were female, and 51% were aged ≥55 years. Through Day 8, no AEs, including infusion-related reactions or hypersensitivity, were reported; 2 participants reported DREs (mild cough, n=2). One SAE (acute myocardial infarction), which was considered unrelated to sotrovimab or COVID-19 by the investigator, occurred on Day 27 and was the only hospitalization reported. Maximum serum concentration (geometric mean) was 745.9 μg/mL. Viral load decreased from baseline through Day 29; only 2 participants (3%) had persistently high viral load (≥4.1 log10 copies/mL) at Day 8. Conclusions: 2000 mg IV sotrovimab was well tolerated, with no new unanticipated safety signals observed.

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Comparison of the risk of hospitalisation among BA.1 and BA.2 COVID-19 cases treated with Sotrovimab in the community in England

Cited by 20 publications

References 6 publications

Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants

Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants

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

Safety, Virology, Pharmacokinetics, and Clinical Experience of High-dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-label Clinical Trial

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