Saliva test for COVID-19
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Our meta-analysis found that the diagnostic sensitivity for saliva NAAT is approximately 83.2% (95% CrI, 74.7%-91.4%), which is comparable to that reported for nasopharyngeal swab NAAT and to the result obtained using our latent class model analysis (84.8%; 95% CrI, 76.8%-92.4%). Given the ease of sample procurement and increased patient comfort, testing centers should strongly consider adopting saliva as their first sample choice, especially in community mass screening programs.
Our study has several strengths. Our search strategy was sensitive, because no additional studies were identified from reference screening or by other means than our primary search strategy. We also addressed a highly clinically relevant question that could potentially rapidly affect global public health policy for testing strategies.
- It is incredibly important to validate this sampling technique for possible deployment in countries or communities with continually high case rates and especially for those with developing health care systems and less access to specialized care.
- An increasingly large number of published studies on the subject suggest that a reliable alternative to nasopharyngeal swab NAAT is clearly being sought. Finally, we used a meta-analysis that accounts for the imperfect reference standard.
- The standard meta-analysis methods would have provided negatively biased estimates of the true specificity of the saliva NAAT, with a larger amount of uncertainty (as can be seen from the prediction intervals). Accounting for this, we were able to obtain a more precise estimate of saliva NAAT diagnostic accuracy.
Our results are limited by the heterogeneity of the included studies, which varied in terms of the study population and the timing of testing. For example, hospitalized and critically ill patients were significantly underrepresented compared with studies performed in the community, and so our results may not apply in this setting. Similarly, many studies compared saliva and nasopharyngeal swabs later in the disease course, and only a few were able to obtain paired samples on the first day of presentation.
Two studies also allowed for repeated samples on multiple days, and correlation between samples may have been imperfectly accounted for, which might have biased our results. However, after removal of these studies in the post hoc analysis, we obtained similar pooled sensitivity and specificity estimates. Furthermore, although each study used assays with similar technology that were all used in clinical practice, small differences between the assays and their targets could have contributed to heterogeneity.
Of note, most studies did not provide details on patient symptoms, and it remains unclear whether certain clinical syndromes (eg, predominantly lower respiratory tract disease or critical illness) may warrant a specific specimen type for optimal NAAT diagnostic accuracy.
Such differences may explain the wide prediction intervals obtained in the traditional meta-analysis (without adjustment for the imperfect reference test), and some caution is warranted in applying the findings of our study to populations that were underrepresented in our meta-analysis. Nevertheless, all latent class meta-analyses showed much less uncertainty in the pooled diagnostic accuracy, including the post hoc analysis in the ambulatory patient population. Hence, despite these limitations, we believe that saliva sampling is a reasonable alternative to nasopharyngeal swabs, especially in community testing centers.
The timing of testing also deserves careful consideration; it is plausible that the timing of testing may have affected the diagnostic accuracy of saliva and nasopharyngeal swab testing differentially. In this review, studies with the highest discordant rates of positive findings for saliva and negative findings for nasopharyngeal swab paired samples included patients with repeated tests performed on multiple days.
This finding suggests that saliva NAAT results may remain positive for longer than nasopharyngeal swab NAAT results. In fact, the 1 study31 we excluded from our meta-analysis, performed exclusively in patients who had clinically recovered from proven COVID-19, found a high rate of positive findings for saliva and negative findings for nasopharyngeal swab paired samples.
This hypothesis has been supported by other studies that compared viral load in saliva and nasopharyngeal specimens and found that more viral RNA could be amplified from saliva than nasopharyngeal swabs and for longer periods. Given that NAAT does not necessarily imply presence of live virus,34 more research is needed to determine the role of saliva NAAT in following viral shedding time, and whether this approach overestimates the duration of infectiousness.
Last, other limitations of saliva NAAT may emerge with time and more widespread use. We, therefore, caution that any large-scale deployment of saliva NAAT should be accompanied by an ongoing rigorous quality control program. Despite these limitations, community testing of presymptomatic or mildly symptomatic persons was well represented in our analyses, and a subgroup analysis limited to this population also demonstrated excellent diagnostic accuracy, implying that saliva NAAT could be deployed in a community setting with a fair level of confidence.
Saliva testing could be particularly useful for larger screening efforts or in patients who are reliable enough to self-report to a testing center (eg, health care workers). Our findings open the door for patient self-collected tests, which would make self-isolation easier to implement and increase community research capacity. In theory, because saliva samples are self-collected, this could also reduce occupational exposures for personnel collecting samples.
This sampling strategy could also conceivably facilitate community prophylaxis and early treatment studies of COVID-19. Importantly, saliva NAAT allows for large-scale testing in high-risk populations that are difficult to reach using hospital-based approaches, an approach that has been deemed to be cost-effective when using nasopharyngeal NAAT. The use of techniques to address inefficiencies, such as saliva testing or pooling of test results, could reduce costs by as much as 40% and personnel by 20%. These populations include college students and children, 2 populations for whom lockdown causes significant harm, but that are also likely to catalyze the spread of the virus. However, these populations and such a testing strategy warrant dedicated studies to better assess the role of saliva NAAT as a public health intervention.
During a pandemic, when the pretest probability of infection is elevated and lack of exposure is unreliable in ruling out COVID-19, large community-based testing programs are required for an effective public health response. Although some questions remain about saliva NAAT diagnostic accuracy in certain populations and settings, especially hospitalized and critically ill patients, saliva NAAT yields a sensitivity and specificity comparable to nasopharyngeal swab NAAT in ambulatory patients presenting with minimal or mild symptoms. Saliva NAAT should therefore be prioritized for larger-scale deployment with prospective studies conducted by clinical microbiology laboratories and public health authorities.
