IntroductionThe COVID-19 pandemic presents unique requirements for accessible, reliable testing, and many testing platforms and sampling techniques have been developed. However, not all test methods have been systematically compared to each other or a common gold standard, and the performance of tests developed in the early epidemic have not been consistently re-evaluated in the context of newly emerging SARS-CoV-2 variants.MethodsWe conducted a repeated measures study with adult healthcare workers presenting for SARS-CoV-2 testing. Participants were tested using seven test modalities: PCR with samples from the nasopharynx, oropharynx, and saliva; and BinaxNOW and iHealth antigen–based rapid detection tests (AgRDT) sampling the oropharynx and the nares. Test sensitivity was compared using any positive PCR test as the gold standard.Results325 individuals participated in the study. PCR tests were the most sensitive with saliva PCR at 0.957 ± 0.048, nasopharyngeal PCR at 0.877 ± 0.075, and oropharyngeal PCR at 0.849 ± 0.082. Standard nasal rapid antigen tests were less sensitive but roughly equivalent at 0.613 ± 0.110 for BinaxNOW brand and 0.627 ± 0.109 for iHealth. Oropharyngeal rapid antigen tests were the least sensitive with BinaxNOW and iHealth brands at 0.400 ± 0.111 and 0.311 ± 0.105 respectively.ConclusionPCR remains the most sensitive testing modality for COVID-19, with saliva PCR being significantly more sensitive than oropharyngeal PCR and equivalent to nasopharyngeal PCR. Saliva testing has patient comfort and financial benefits, making it a preferred testing modality. Nasal AgRDTs are less sensitive than PCR though more accessible and convenient.