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PurposeEmerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have impacted the in vitro activity of sotrovimab 500 mg, with reduced fold change in EC50for the Omicron BA.2 sublineage and onward. The correlation between this reduction and clinical efficacy outcomes is unknown. In the absence of clinical trials assessing the efficacy of sotrovimab against emerging variants, real-world evidence becomes a critical source of information. A systematic literature review (SLR) of published observational studies was undertaken to evaluate the effectiveness of sotrovimab on severe clinical outcomes during the Omicron BA.2 subvariant predominance period.MethodsSearches of indexed electronic databases for peer-reviewed journals, preprint articles, and conference abstracts published between January 1, 2022 and November 3, 2022 were undertaken using a combination of search terms for COVID-19, sotrovimab, and observational study design. Study quality was assessed using the Newcastle Ottawa Scale (NOS).ResultsFrom the 343 unique titles and abstracts identified, five studies were eligible for inclusion in the SLR. Included studies displayed heterogeneity in study design and population. The OpenSAFELY study, which received a high NOS score and had a sufficient sample of patients treated with sotrovimab during BA.2 predominance, demonstrated clinical effectiveness during both BA.1 (adjusted hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.33–0.88;p= 0.014) and BA.2 (adjusted HR 0.44, 95% CI 0.27–0.71;p= 0.001) periods vs molnupiravir. Furthermore, a US-based study that also received a high NOS score reported that sotrovimab was associated with a lower risk of 30-day all-cause hospitalization or mortality compared with no monoclonal antibody treatment during the BA.2 subvariant surge in March (adjusted relative risk (RR) 0.41, 95% CI 0.27–0.62) and April 2022 (adjusted RR 0.54, 95% CI 0.08–3.54). Although only a limited number of studies evaluated sotrovimab during both the BA.1 and BA.2 periods, these demonstrated that clinical outcomes in patients with COVID-19 treated with sotrovimab were consistently low across both periods. One large study directly compared data from the two periods and found no evidence of a difference in the clinical outcomes of sotrovimab-treated patients with sequencing-confirmed BA.1 and BA.2 (HR 1.17, 95% CI 0.74–1.86).ConclusionThe observational data presented in this SLR provide evidence that the effectiveness of sotrovimab (IV 500 mg) is maintained against Omicron BA.2 in both ecological and sequencing-confirmed studies, either through the demonstration of low and comparable rates of severe clinical outcomes between the Omicron BA.1 and BA.2 periods, or by comparison against an active comparator or no treatment within the Omicron BA.2 period.Key pointsWhy carry out this study?Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab 500 mg, with reduced fold change in EC50relative to wild-type for the Omicron BA.2 sublineage and onward; the clinical relevance of this difference on outcomes for BA.2 (and other variants) is unknown.Given the complexity of generating formal clinical trial data in the context of the constantly evolving SARS-CoV-2 landscape, real-world evidence is a key source of information with which to assess the effectiveness of treatments such as sotrovimab on newly predominant or emerging variants.We conducted a systematic literature review to evaluate the effectiveness of sotrovimab for the early treatment of COVID-19 on clinical outcomes during the period predominated by the Omicron BA.2 subvariant.What was learned from the study?Sotrovimab treatment was associated with low proportions of severe clinical outcomes (such as all-cause or COVID-19-related hospitalization or mortality) in patients infected during periods of Omicron BA.2 predominance, despite reduction in the in vitro neutralization activity of sotrovimab.These data support continued clinical effectiveness of sotrovimab during Omicron BA.2 predominance. |
