Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK

Antigen-detection rapid diagnostic tests (Ag-RDTs) have become a central pillar for the management of COVID-19 worldwide due to their speed and ease of use, and are now being developed for use in other emerging outbreaks. Like other viruses, SARS-CoV-2 is subject to rapid mutation as it spreads, and new Variants of Concern (VOCs) emerge frequently, posing a significant challenge for the reliability of Ag-RDTs designed against the original strain to detect newer, highly mutated variants. It is therefore important that the performance of Ag-RDTs is regularly evaluated, particularly in outbreak scenarios where rapid diagnostics are key to limiting disease spread. Here, we present a comprehensive evaluation of the analytical and clinical sensitivity of 34 commercially available Ag-RDTs with five VOCs, all of which were highly prevalent in the UK at various times between 2019 and 2023. This evaluation highlights the importance of regular evaluation of Ag-RDT performance, with several Ag-RDTs demonstrating reduced performance with some VOCs. This study also highlights the challenges that arise when different organisations lack a consensus approval threshold, causing confusion over Ag-RDT performance and making it difficult to properly evaluate individual tests. We conclude that regular performance evaluation through our proposed pipeline combined with a broad consensus approval threshold across global organisations is essential to maintaining the effectiveness of Ag-RDTs as a disease management tool during outbreaks. ImportanceAntigen-detection rapid diagnostic tests (Ag-RDTs) came to global prominence during the COVID-19 pandemic, where they offered a quick and simple at home diagnostic which could be used to manage disease spread. A major ongoing challenge for the broad use of Ag-RDTs is the speed at which new SARS-CoV-2 variants emerge, each of which has the potential to reduce the performance of the available Ag-RDTs. As Ag-RDTs are explored for use in other viral disease outbreaks, pipelines for the regular evaluation of test performance are essential for ensuring that Ag-RDTs can be employed effectively. Here, we have developed a robust pipeline for the large-scale evaluation of commercially available Ag-RDTs against several major SARS-CoV-2 variants, which can be adapted and applied to other emerging outbreaks to ensure test performance is maintained as a virus evolves.