Microbiol Spectr. 2023 Oct 13:e0176823. doi: 10.1128/spectrum.01768-23. Online ahead of print.
The continuous genetic evolution of SARS-CoV-2 resulting in the immune escape variant of concern (VoC) Omicron poses a challenge to rapid and accurate diagnosis of infection, especially in high-risk groups such as healthcare workers. We performed a clinical study to determine the diagnostic accuracy and robustness of a second-generation rapid antigen test compared to a first-generation rapid antigen test with an RT-qPCR-based assay as gold standard, for early detection of infections with SARS-CoV-2 Omicron VoC. A total of 428 healthcare workers with COVID-19-associated symptoms or during routine testing participated in the study and completed a questionnaire on infection-associated symptoms, previous SARS-CoV-2 infections, and vaccination status. All participants performed a second- and first-generation rapid antigen test on the day of presentation and repeated the test 2 days later, and a diagnostic SARS-CoV-2 RT-qPCR assay was performed. qPCR-confirmed SARS-CoV-2 infections (n = 104) with Omicron VoC (BA.2, BA.4, BA.5) were detected by the first-generation rapid antigen test with a sensitivity of 83.7% (95% CI 75.12%-90.18%), whereas the second-generation rapid antigen test performed with a sensitivity of 89.4% (95% CI 81.9%-94.6%). Increased sensitivity of the second-generation rapid antigen test led to earlier detection of SARS-CoV-2 infection, while lower test sensitivity of the first-generation rapid antigen test was compensated by repeated testing 2 days later. Moreover, direct in vitro comparison revealed a lower limit of detection for the second-generation rapid antigen test for isolates of currently circulating Omicron sub-lineages BA.5.2, BQ.1, and XBB.1. IMPORTANCE The results from this study demonstrate the usefulness of a second-generation rapid antigen test for early detection of infection with the SARS-CoV-2 Omicron variant of concern (VoC) and reveal a higher sensitivity to detect immune escape Omicron VoCs compared to a first-generation rapid antigen test (89.4% vs 83.7%) in the high-risk group of healthcare workers.