Introduction During the COVID-19 pandemic, SARS-CoV-2 antigen rapid detection tests (RDTs) emerged as point-of-care diagnostics in addition to the RT-qPCR as the gold standard for SARS-CoV-2 diagnostics. Facing the course of the COVID-19 pandemic to an endemic characterised by several SARS-CoV-2 virus variants of concern (VOC) and an increasing public COVID-19 vaccination rate the aim of the study was to investigate the long-term test performance of SARS-CoV-2 RDT in large-scale, clinical screening use during and its influencing factors, above all SARS-CoV-2 VOC and COVID-19 vaccination. Methods In a prospective performance assessment conducted at a single centre tertiary care hospital, RDTs from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to RT-qPCR among individuals aged ≥6 month. The evaluation involved the determination of standardised viral load from oropharyngeal swabs as well as the evaluation of their influencing factors, especially the COVID-19 vaccination, for detecting SARS-CoV-2 in a clinical point-of-care environment spanning from 12 November 2020 to 30 June 2023 among patients, staff, and visitors of the hospital. Results Among the 78,798 RDT/RT-qPCR tandems analysed, 2,016 (2.6%) tandems tested positive for SARS-CoV-2, with an overall sensitivity of 34.5% (95% CI 32.4-36.6%). A logistic regression revealed that typical COVID-19 symptoms significantly declined over the course of the study and throughout the COVID-19 pandemic, and that among the vaccinated, significantly fewer presented with an infection exhibiting typical symptoms. The employed lasso regression model indicated that only higher viral load and typical COVID-19 symptoms significantly increase the likelihood of a positive RDT result in the case of a SARS-CoV-2 infection directly. Conclusion Our findings indicate that only viral load and COVID-19 symptoms directly influence RDT performance while the obtained effects of COVID-19 vaccination and Omicron VOC both reducing RDT performance were mediated by these two factors. RDTs remain an adequate diagnostic tool for detecting SARS-CoV-2 in individuals showing respiratory symptoms. RDTs show promise beyond SARS-CoV-2, proving adaptable for detecting other pathogens like Influenza and RSV, highlighting their ongoing importance in infection control and prevention efforts.

Manuel Krone receives honoraria from Abbott outside of the submitted work. None of the other authors have any conflicts of interest to declare.

This study was partially funded by the German Federal Ministry of Education and Research (BMBF) as part of the Network University Medicine (NUM): NaFoUniMedCovid19 Grant No: 01KX2021, Project: B-FAST as well as by COVID-19 research funds from the Free State of Bavaria provided to the Julius-Maximilians-Universität Würzburg, Germany. This work was supported by Bay-VOC (Bavarian State Ministry of Health and Care). Nils Petri was supported by the UNION CVD scholarship funded by the German Research Foundation (DFG).

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