Real-World Severe COVID-19 Outcomes Associated with Use of Antivirals and Neutralising Monoclonal Antibodies: A Population-Based Retrospective Cohort Study in Scotland

Background: We sought to investigate the incidence of severe COVID-19 outcomes after treatment with antivirals and neutralising monoclonal antibodies, and estimate the comparative effectiveness of treatments in community-based individuals.Methods: We conducted a retrospective cohort study investigating clinical outcomes of hospitalisation, intensive care unit admission and death, in those treated with antivirals and monoclonal antibodies for COVID-19 in Scotland between December 2021 and September 2022. We compared the effect of various treatments on the risk of severe COVID-19 outcomes, stratified by most prevalent sub-lineage at that time, and controlling for comorbidities and other patient characteristics.Findings: We identified 14,368 individuals treated for COVID-19 during our study period, some of whom were treated for multiple infections. The incidence of severe outcomes (inpatient admission or death) in community-treated patients (80% of all treatment episodes) was 1.2% (n=140/11717, 95% CI 1.0-1.4), compared to 33.9% in those treated in hospital for acute COVID-19 (re-admissions or death; n=42/124, 95% CI 26.1-42.5). For community-treated patients, there was a lower risk of severe outcomes (inpatient admission or death) in younger patients, and in those who had received three or more COVID-19 vaccinations. During the period in which BA.2 was the most prevalent sub-lineage in the UK, sotrovimab was associated with a reduced treatment effect compared to Paxlovid. However, since BA.5 has been the most prevalent sub-lineage in the UK, sotrovimab was the treatment associated with the lowest incidence of severe outcomes.Interpretation: Around 1% of those treated for COVID-19 with antivirals or neutralising monoclonal antibodies required hospital admission. During the period in which BA.5 and BA.1 were the most prevalent sub-lineages in the UK, sotrovimab was associated with the lowest incidence of severe outcomes in community-treated patients. While BA.2 was most prevalent, Paxlovid treatment was associated with the lowest incidence. Funding: Medical Research Council [grant number UKRIMC_PC19075] and the National Institute for Health and Care Research [award number NIHR135575].Declaration of Interest: AS has served on COVID-19 Advisory Groups for the UK and ScottishGovernments and AstraZeneca, all of which have been unremunerated. He holds a research grant on the effectiveness and safety of mABs from GS. All others have nothing to declare. Ethical Approval: Data approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201), and Public Benefit and Privacy Panel for Health and Social Care (reference number: 0920-0279).