Real-world Effectiveness of Sotrovimab for the Treatment of SARS-CoV-2 Infection During Omicron BA.2 and BA.5 Subvariant Predominance: a Systematic Literature Review

Background Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab, with variable fold changes in neutralization potency reported for Omicron BA.2 and subsequent variants. We performed a systematic literature review (SLR) to evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance. Methods Electronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022–February 27, 2023. Results The 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions, and comprised >1.7 million high-risk patients with COVID-19, of whom approximately 41,000 received sotrovimab (range n=20– 5979 during BA.2 and n=76–1383 during BA.5 predominance). Studies were from the US, UK, Italy, Denmark, France, Qatar, and Japan. Four studies compared the effectiveness of sotrovimab with untreated or no monoclonal antibody treatment controls, two compared sotrovimab with other treatments, and three single-arm studies compared outcomes during BA.2 and/or BA.5 versus BA.1. The remaining five studies descriptively reported rates of clinical outcomes in patients treated with sotrovimab. Rates of COVID-19-related hospitalization or mortality among sotrovimab-treated patients were consistently low (0.95% to 4.0% during BA.2; 0.5% to 2.0% during BA.5). All-cause hospitalization or mortality was also low (1.7% to 2.0% during BA.2; 3.4% during combined BA.2 and BA.5 periods). During BA.2, a lower risk of all-cause hospitalization or mortality was reported across studies with sotrovimab versus untreated cohorts. Compared with other treatments, sotrovimab was associated with a lower (molnupiravir) or similar (nirmatrelvir/ritonavir) risk of COVID-19-related hospitalization or mortality during BA.2 and BA.5. There was no significant difference in outcomes between the BA.1, BA.2 and BA.5 periods. Conclusions The studies included in this SLR suggest continued effectiveness of sotrovimab in preventing severe clinical outcomes during BA.2 and BA.5 predominance, both against an active/untreated comparator and compared with BA.1 predominance. ### Competing Interest Statement MB is a contracted worker for GSK. EJL, DCG and MD are employees of, and/or stock/shareholders in, GSK. CR and LL are employees of PPD Evidera, which received funding from GSK and Vir Biotechnology, Inc to conduct the study. ### Funding Statement This study was funded by GSK in collaboration with Vir Biotechnology, Inc (study number 220061). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Only publicly available papers were included in this SLR, and no human subjects were involved; ethics approval was therefore not required. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes