Comparison of the performance of SARS-CoV-2 RNA qRT-PCR testing based on expectorated and drooled saliva samples

Abstract Purpose Saliva has been considered a suitable sample material for SARS-CoV-2 testing but uncertainty remained regarding the sensitivity and reliability of different saliva collection methods for community mass testing. This study aimed to investigate the potential utility of expectorated saliva (ES) and drooled saliva (DS) through a large cohort study. Methods ES and DS samples were collected in a two-stage non-randomized prospective cohort study. Their utility for SARS-CoV-2 RNA qRT-PCR testing was assessed by comparison with results for combined throat and nose (CTN) swabs. A total of 2,878 subjects were recruited, from which 2,747 were evaluable for statistical analyses. Results Using CTN swab-based results as reference,DS- and ES-based tests showed the same high level of concordance (98% vs 98%) or specificity (99% vs 99%). Sensitivity seemed to be higher for DS than for ES (93% vs 80%) but not significantly once viral concentration was taken into account. Multivariable analysis indicated however an inferior sensitivity of saliva-based testing for female compared to male subjects with low viral burden. Assuming no false positive qRT-PCR results, an unbiased comparison showed no significant difference in sensitivity between saliva- and swab-based testing. Conclusion SARS-CoV-2 RNA testing based on saliva showed high diagnostic accuracy and can be considered an alternative where swabbing may not be tolerated or operationally feasible. Drooled saliva yielded the same diagnostic performance compared to expectorated saliva and may present a preferred option with reduced aerosol risk and increased compliance. Observed sex-specific difference in detection performance however warrant further investigations.