Saliva and Oral Swabs Emerge as Scalable Alternative to Nasopharyngeal SARS-CoV-2 Testing

The standard method for detecting upper respiratory viruses is to perform tests on tissue sample from the back of the sinus cavity collected by inserting a long nasopharyngeal swab deep into the patient’s nostril. However, when the COVID-19 pandemic first broke out across the country, the obstacles to implementing testing using such sample collection methods on a mass scale quickly became clear. The good news is that as the pandemic drags into its ninth month, COVID-19 testing on saliva samples is starting to emerge as a workable alternative. The Diagnostic Challenge There are three things about nasopharyngeal sample collection that impair its viability as a method for broad and widespread testing during the pandemic:

• It is uncomfortable for patients;
• It must be performed by a skilled health professional using appropriate personal protective equipment; and
• It requires swabs and chemicals which are currently in short supply.

As the pandemic spread, researchers began investigating cheaper, simpler alternatives for sample collection, including home collection kits and saliva-based tests. The Case for Saliva-Based Testing Among the nearly 200 COVID-19 diagnostic tests to receive Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA), nearly a dozen may be performed on saliva samples provided directly by the patient without the need for a health care professional. Like tests using swabs, saliva tests are based on polymerase chain reaction (PCR) technology, which amplifies small amounts of viral genetic material to facilitate detection. Some of the saliva tests to receive EUA, including assays from Yale and the University of Illinois, simplify the process by eliminating a standard intermediate step: the extraction of viral RNA. Their protocols also do not require viral transport media (VTM), the chemicals used to stabilize the samples after collection. While nobody disputes that saliva testing is cheaper, simpler and easier on the supply chain, there are concerns about its accuracy as compared to testing on samples obtained by nasopharyngeal swabs. However, evidence is emerging to suggest that COVID-19 saliva-based is at least as reliable and accurate as swab-based testing. A Yale University study published in The New England Journal of Medicine on August 28 found that the Yale saliva test actually detected the SARS-CoV-2 virus more frequently in patients known to have COVID-19, with 81 percent of the tests coming back positive in the first five days of infections, compared to the 71 percent rate got nasopharyngeal tests. The saliva test also detected more copies of the virus’s genetic material. A second study from the University of Ottawa published in the Annals of Internal Medicine the very same day was also supportive of saliva testing. The researchers tested nearly 2,000 people who had either mild symptoms of the virus or no symptoms but were at a high risk of infection. Participants collected their own saliva and also underwent the traditional swab test: 34 came back positive in both tests. In 14 cases, the virus was detected in the saliva sample, but not the nasal sample. In 22 cases, the opposite was true. Although the nasal sample had a slight edge in detecting infections, the researchers concluded that the study findings support the case for use of saliva samples to diagnose SARS-CoV-2. The Case for Oral Swab-Based Testing Another alternative testing technique uses specimens collected by oral rather than nasopharyngeal swabs. Respiratory viruses colonize areas inside the nasal cavity and at the back of the throat. Besides the nasopharyngeal approach, nasal samples obtained with shorter and less invasive swabs have proven effective for COVID-19 testing. Unlike nasopharyngeal swabs, patients can self-swab, and the oral swab procedure takes less time to perform than a saliva test. However, unlike saliva tests, oral swab tests generally do require the involvement of a qualified health care professional. A case study for the effectiveness of oral swab testing comes from the City of Los Angeles, which began using the Curative-Korva SARS-Cov-2 Assay, an oral swab test developed by Korva Labs. More than 10,000 samples have been collected per day since the City first started using the assay in late March (the test received EUA from the FDA on April 17) with Curative’s three labs processing the tests. Takeaway Eight months into the pandemic, the move toward saliva and oral swab testing is gaining traction, with tens of thousands of people across the country undergoing such testing each day. However, saliva and oral swab tests still represent only a small percentage of the more than 900,000 tests conducted daily on average at the end of September. One reason for the slow adoption is the inherently caution displayed by regulators, payors and clinicians toward new and unproven technologies and understandable predilection and preference for well-established protocols.