Saliva sampling matters for salivary diagnostics of viral infections

Saliva, a non-invasive biofluid with a variety of biomolecules, has been increasingly recognized as a reliable specimen in the diagnostics of viral infections. Compared to the standard specimens represented by blood and nasopharyngeal swab, saliva is advantageous in non-invasive, simple collection, convenient storage and compatibility with self-testing and large-scale screening. Saliva is an all-round specimen for viral detection as the shedding of viral nucleic acid fragments, antigens and the secretion of virus-specific antibodies are present in saliva. Accordingly, saliva has been widely used to detect a variety of viruses, including saliva-borne, air-borne and blood-borne transmitted viruses. However, challenges also arise as diverse methods during collection, storage and processing of the saliva could lead to discordant results among different studies. It is now aware that the methodology of saliva sampling is critical to the detection of viral biomarkers in the accuracy, repeatability and consistence with the data retrieved from the standard specimens. Therefore, establishing a standardized procedure for saliva sampling is crucial. Here we focus on a dozen factors that may affect the results of salivary diagnostic of viral infections and suggest a set of standardized procedures for saliva sampling, aiming to minimize result variation and benefit the application of saliva in salivary diagnostics of viral infections.