Saliva as alternative to naso-oropharyngeal swab for SARS-CoV-2 detection by RT-qPCR: a multicenter cross-sectional diagnostic validation study

Saliva has been demonstrated as feasible alternative to naso-oropharyngeal swab (NOS) for SARS-CoV-2 detection through reverse transcription quantitative/real-time polymerase chain reaction (RT-qPCR). This study compared the diagnostic agreement of conventional NOS, saliva with RNA extraction (SE) and saliva without RNA extraction (SalivaDirect) processing for RT-qPCR in identifying SARS-CoV-2. All techniques were also compared, as separate index tests, to a composite reference standard (CRS) where positive and negative results were defined as SARS-CoV-2 detection in either one or no sample, respectively. Of 517 paired samples, SARS-CoV-2 was detected in 150 (29.01%) NOS and 151 (29.21%) saliva specimens. The saliva-based tests were noted to have a sensitivity, specificity and accuracy (95% confidence interval) of 92.67% (87.26%, 96.28%), 97.55% (95.40%, 98.87%) and 96.13% (94.09%, 97.62%), respectively, for SE RT-qPCR and 91.33% (85.64%, 95.30%), 98.91% (97.23%, 99.70%) and 96.71% (94.79%, 98.07%), respectively, for SalivaDirect RT-qPCR compared to NOS RT-qPCR. Compared to CRS, all platforms demonstrated statistically similar diagnostic performance. These findings suggest that both conventional and streamlined saliva RT-qPCR are at least non-inferior to conventional NOS RT-qPCR in detecting SARS-CoV-2.