AbstractThe COVID-19 pandemic has been hallmarked by several waves of variants of concern (VoCs), each with novel challenges. Currently, the highly transmissible Omicron VOC is predominant worldwide, and sore throat is common among other cold-like symptoms. Anecdotes on social media suggested sampling one’s throat can increase sensitivity for Omicron detection by antigen-based rapid testing devices (Ag-RDTs). This work determines whether the sensitivity of Ag-RDTs designed for nasal sampling is altered with use of self-administered throat swabs in self-perceived asymptomatic individuals. This investigation compared results of a common Ag-RDT (i.e. Abbott Panbio COVID-19 Ag Rapid Test Device) using three sampling sites: nasal swab; throat swab and; combined nasal/throat. All Ag-RDT results were confirmed with molecular testing. Compared to RT-PCR, samples from nasal or throat swabs each detected 64.5% of SARS-CoV-2 cases; however, combining the contributions of each swab increased sensitivity to 88.7%. This trend was also evident with the Rapid Response Ag-RDT (BTNX), which uses a more flexible swabs than Panbio. When nasal swab collection was compared to paired sampling of the nasal/throat using a single swab with the Panbio Ag-RDT, the sensitivity of each was 68.4% and 81.6%, respectively. No false-positive results were observed with nasal, throat, or combined nasal/throat sampling. Self-administered throat and nasal/throat swabs both had >90% acceptability. These findings support the use of self-collected combined nasal/throat sampling for Ag-RDT based SARS-CoV-2 detection in self perceived asymptomatic individuals.