Public health experts emphasize the need for quick, point-of-care SARS-CoV-2 detection as an effective strategy for controlling virus spread . To this end, many``antigen"detection devices were developed and commercialized . These devices are mostly based on detecting SARS-CoV-2's nucleocapsid protein . Recently, alerts issued by both the FDA and the CDC raised concerns regarding the devices' tendency to exhibit false positive results . In this work, we developed a novel alternative spike-based antigen assay, comprising four high-affinity, specific monoclonal antibodies, directed against different epitopes on the spike's S1 subunit . The assay's performance was evaluated for COVID-19 detection from nasopharyngeal swabs, compared to an in-house nucleocapsid-based assay, composed of novel antibodies directed against the nucleocapsid . Detection of COVID-19 was carried out in a cohort of 284 qRT-PCR positive and negative nasopharyngeal swab samples . The time resolved fluorescence (TRF) ELISA spike assay displayed very high specificity (99 %) accompanied with a somewhat lower sensitivity (66% for Ct <25), compared to the nucleocapsid ELISA assay which was more sensitive (85% for Ct <25) while less specific (87% specificity). Despite being outperformed by qRT-PCR, we suggest that there is room for such tests in the clinical setting, as cheap and rapid pre-screening tools . Our results further suggest that when applying antigen detection, one must consider its intended application (sensitivity vs specificity), taking into consideration that the nucleocapsid might not be the optimal target . In this regard, we propose that a combination of both antigens might contribute to the validity of the results . Schematic representation of sample collection and analysis . The figure was created using BioRender.com.