0818 SalivaDirect
BioCentury

Product Development

SalivaDirect slots into growing matrix of resource-saving COVID-19 tests

How Yale’s SalivaDirect compares with other strategies to expand COVID-19 testing

How the benefits of Yale’s SalivaDirect compare with those of other strategies to expand COVID-19 testing

Aug 18, 2020 | 10:45 PM GMT

Yale’s SalivaDirect is the latest FDA-authorized test geared to expand COVID-19 detection by shrinking cost and supply chain issues. The molecular test is most distinguished from other resource-saving strategies by being optimized for saliva from the get-go, with benefits that go beyond avoiding uncomfortable swabs.

On Saturday, FDA authorized SalivaDirect to detect SARS-CoV-2 RNA in saliva  from individuals suspected by a healthcare provider to have COVID-19. The open-source protocol can be used on a variety of reagents and instruments from different vendors, though it must be performed in a high complexity CLIA lab.

Researchers from Yale University brought down the cost of the reverse transcription polymerase chain reaction (RT-PCR)-based test by eliminating the need for specialized sample collection tubes containing preservatives, and by replacing the cumbersome and reagent-strapped RNA extraction process with a simpler step involving heat and the inexpensive enzyme proteinase K. 

In addition to making frequent testing more palatable, optimizing the test for saliva samples conserves resources by reducing the need for nasal swabs sticks, skilled personnel to collect samples, and personal protective equipment (PPE) for those personnel — all of which are in limited supply.

Data submitted to FDA show the test had 94.6% sensitivity and 100% specificity on 37 samples deemed positive and 30 samples deemed negative by a conventional RT-PCR test. SalivaDirect’s limit of detection -- the lowest amount of target a test can detect at least 95% of the time -- ranged from 6,000 to 12,000  RNA copies per mL depending on the instruments and reagents used, in line with other FDA-authorized tests, albeit on the lower end of sensitivity (see “Limits of Detection for COVID-19 Diagnostics”).

The backlogs in conventional RT-PCR diagnostics, combined with growing calls for broad asymptomatic screening, are pushing resource-saving technologies such as pooled RT-PCR, antigen tests and loop-mediated isothermal amplification (LAMP) to the fore, with the typically lower sensitivity of these technologies increasingly viewed as an acceptable trade-off (see “Point-of-Care, Pooled Tech as Way Out of Testing Crunch”; “Asymptomatic Testing Pushes Forward”).

BioCentury

SalivaDirect’s benefits are most similar to those of pooled testing, in that both approaches reduce the costs and supplies required to conduct RT-PCR tests, and both can be readily applied to widely available instruments, including high-throughput systems. FDA has authorized four RT-PCR COVID-19 tests for use on pooled samples, with the caveat that they are best deployed in low prevalence settings (see “EUA for Pooled Test Points to Effect of Prevalence”).

Both strategies still require centralized laboratory infrastructure, and therefore have turnaround times of 24 hours or more. In contrast, rapid antigen tests and LAMP technologies share even fewer resources with conventional RT-PCR, and deliver results in less than an hour at the point-of-care.

FDA has authorized point-of-care antigen tests from Becton Dickinson and Co. (NYSE:BDX) and Quidel Corp. (NASDAQ:QDEL), and a lab-based LAMP test from Color Genomics Inc. 

Both FDA-authorized antigen tests use individual lateral flow cartridges, which are relatively cheap to produce at scale, but limited in throughput compared with automated lab tests. However, the underlying immunoassay technology could be adapted to high-throughput  instruments common in labs. 

Color runs its test on a high-throughput system, but its automated LAMP workflow has less precedent in most labs than RT-PCR and immunoassays. The technology, which is distinguished from PCR by its lack of temperature cycling, has primarily been framed as a simple, inexpensive strategy that can be used in the field (see “LAMP in Zika Diagnostic”).

While pooled, antigen and LAMP tests could theoretically be applied to saliva samples, FDA has not yet authorized these technologies for that use. 

On July 29, Sorrento Therapeutics Inc. (NASDAQ:SRNE) announced it had licensed a rapid, point-of-care LAMP test to detect SARS-CoV-2 RNA in saliva samples; the technology, developed at Columbia University and described in a June medRxiv preprint, is under FDA review.

How to gain access

Continue reading with a
two-week free trial.