Diagnostic accuracy of non-invasive SARS-CoV-2 screening tests: a national prospective analysis

Background Providing non-invasive, accurate and affordable SARS-CoV-2 tests represents a public health priority, to better control viral circulation while protecting healthcare workers. Saliva is a robust alternative to nasopharyngeal (NP) swab, but there is heterogeneity in collection and pre-analytical methods. Methods Relying on a national COVID-19 Public Health Programme, we prospectively recruited 3,488 symptomatic and asymptomatic adults attending the Monaco community centre for NP RT-PCR testing from February 2021-2023. Saliva was concomitantly obtained with either a buccal swab or an oral sponge (OS) and analysed by an RT-PCR assay and a fully automated electrochemiluminescent enzyme immunoassays (ECLIA) rapid antigen test (RAT). Results Sensitivity of the buccal RT-PCR varied according to previous SARS-CoV-2 infection, vaccination, and presence of symptoms, while it remained around 95% for the OS RT-PCR. Specificity of the buccal RT-PCR approached 100% and was around 95% for the OS-RT PCR. The RAT sensitivity was 66.9% and 69.1% comparing to NP and OS RT-PCR assays and rose to 71% and 97% in case of a high viral load (Ct<25), respectively. Conclusions OS for sampling saliva using RT-PCR assay showed high accuracy amongst symptomatic and non-symptomatic adults, including the identification of negative nasopharyngeal swabs. This method allows self-collection without any prior conditions for the patient nor laboratory pre-analytical step. The ECLIA RAT presents high throughput at moderate cost and could be relevant in a mass screening strategy or settings where diagnostic capacity is limited. Our findings encompassed the latest SARS-CoV-2 omicron subvariants, such as BA.4&5 and the XBB series.