Self-Collected Oral Fluid Saliva Is Insensitive Compared With Nasal-Oropharyngeal Swabs in the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Outpatients

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared with the nasopharyngeal swab.

Methods: We compared real-time reverse-transcription polymerase chain reaction Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a nonhospitalized, ambulatory cohort of coronavirus disease 2019 (COVID-19) patients at multiple time points. These 2 sentences should be at the beginning of the results.

Results: There were 171 matched specimen pairs. Compared with nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid percent collection device increased the percent positive agreement from 37.2% (16 of 43) to 44.6% (29 of 65). The positive percent agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample.

Conclusions: In this study of nonhospitalized SARS-CoV-2-infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared with nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection and the time from symptom onset especially in outpatient populations.

Keywords: COVID-19; SARS-CoV-2; coronavirus; outpatient; saliva.

Figure 1.

Forest plot of the positive percent agreement of salivary sample types compared with nasopharyngeal swab. Asterisks denote outpatient studies.

Figure 2.

Cycle thresholds (CT) are plotted for matched nasal-oropharyngeal (OP) swab and oral fluid real-time reverse-transcription polymerase chain reaction. Viral burdens that were higher in nasal-OP or oral fluid are shown in blue and red lines, respectively, in (A) all matched specimens, (B) oral fluid only, and (C) oral fluid plus the addition of spit. Samples that were negative in both sample types are not shown.

Figure 3.

The proportion of nasal-oropharyngeal (OP) and oral fluid matched specimens that were positive in participants who are 1–5 days, 6–10, and more than 11 days after symptom onset in samples from participants where the date of symptom onset could be determined. Eight participants without a date of symptom onset (19 specimen pairs) are not included in this figure. RT-PCR, reverse-transcription polymerase chain reaction.

Figure 4.

(A) Cycle threshold values are shown for individual participants over time. Blue lines denote decreasing viral burden, whereas red lines represent increasing viral burden with increasing number of days after symptom onset in oral fluid. Samples where spit was added are shown in the open circles, and those with oral fluid only are in the black circles. and (B) nasal-oropharyngeal (OP) specimens.