Given the numerous specimen types and collection devices, it is critically important to measure their performance characteristics before considering them suitable for clinical use. Consequences of false positives may induce stress for patients and families, impact daily life (e.g. job/schooling) and initiate unnecessary isolation precautions. Conversely, a false-negative result may lead to increased transmission as the suspected patient fails to isolate or quarantine . These characteristics include analytical sensitivity, which is the percentage of true positives a test accurately captures. Analytical specificity is the percentage of true negatives a test accurately captures. Ideally, a test should be both highly sensitive and specific to minimize false positives and false negatives. The performance should be measured against a gold standard test or procedure, which at this point in time continues to be NPS.
Performance characteristics of saliva as an alternative specimen for SARS-CoV-2 detection
Despite the approval of different alternative specimen types in addition to NPS, many still rely on collection swabs, UTM and personal protective equipment (PPE) to protect healthcare workers. Saliva as a specimen type has garnered huge interest because to its simplicity of collection as it can be self-collected without the need for swabs and transport media and reduces the need for PPE. Additionally, high ACE-2 receptor expression has been demonstrated in salivary glands making saliva an appropriate specimen also from a pathophysiological perspective.
Meta-analyses of greater than 46 studies compared the performance characteristics of saliva specimens to other specimen types and reported that detection of SARS-CoV-2 in saliva is comparable to NPS [5, 8, 9]. The sensitivities were 88% (95% CI: 81–93%), and 94% (95% CI: 90–98%), respectively. Interestingly, the performance of saliva was superior to ANS (82%, 95% CI: 73–90%) and OPS (84%, 95% CI: 57–100%) .
The presence or absence of symptoms at the time of testing had minimal effect on test performance. In asymptomatic and symptomatic patients, the sensitivities of saliva were 87% (95% CI: 70–98%) and 88% (95% CI: 79–95%), respectively. Similar to NPS, the ability to detect SARS-CoV-2 in saliva decreased at 7 days post-symptoms onset [>7 days: 74% (95% CI: 62–85%) versus ≤7 days 89% (95% CI: 73–99%)]. Importantly, many studies have reported SARS-CoV-2 detection from saliva even when other specimen types are negative, further supporting its use as a reliable specimen type. Specificity of both saliva and NPS are high at 99% (95% CI: 98–99%) and 98% (95% CI: 97–99%), respectively . Given the increased costs associated with collection systems that include swabs and transport media, collection of saliva, particularly raw saliva samples, has been projected to have economic benefits if more widely used. One study estimates that at least US$600¦000 can be saved per 100¦000 people if saliva were used in lieu of NPS . Additionally, pooling of saliva samples, particularly when used for surveillance testing in asymptomatic populations, may further reduce cost with minimal effects of performance .
Admittedly, the majority of studies have focused on the adult populations and only a few were dedicated to pediatric populations, often with small sample sizes. One study with a larger sample size (n=43 children) demonstrated comparable performance of saliva compared to NPS . The overall concordances of saliva and NPS were 91.0% (273/300) and 94.7% (284/300), respectively. Performance of saliva (82.4%) and NPS (85.3%) was comparable when only first-time-positive pediatric patients were analysed regardless of clinical presentation (presence or absence of symptoms) and no significant differences in viral load were observed .
There are numerous approaches to saliva collection which may affect overall detection ability. Instructing patients to cough or clear their throats before saliva collection may be more effective than passive drooling or spitting as the former allows for representation of lower respiratory sample alongside saliva; however, the introduction of coughing may increase risk to healthcare workers . Meanwhile, patients who avoided eating, drinking, or brushing teeth before saliva collection had a higher detection yield [91% (95% CI: 86–95%) vs 86% (95% CI: 79–92%)]. Additionally, sensitivity was found to be higher when saliva collection was supervised [86% (95% CI: 72–93%) vs 66% (95% CI: 50–80%), respectively] .