SARS-CoV-2 Saliva Testing Gains Traction
Saliva testing for the virus that causes COVID-19 is gaining acceptance in both the scientific community and US market.
Saliva-based SARS-CoV-2 tests emerged as an alternative COVID-19 diagnostic early during the COVID-19 public health emergency (PHE) when the nasopharyngeal swabs used to collect tissue samples for conventional tests were in desperately short supply. While saliva test kits and products received FDA Emergency Use Authorization (EUA) during the crisis, saliva testing has had only a marginal impact. But that may be about to change now that the agency has, for the first time, cleared a SARS-CoV-2 saliva test for over-the-counter use.
The Advantages of Saliva Testing
The principal method of detecting the SARS-CoV-2 virus is to perform polymerase chain reaction (PCR) tests capable of detecting RNA from the virus. PCR tests are high in specificity and sensitivity. But they must be performed on tissue samples collected from the back of the sinus cavity by inserting a long nasopharyngeal swab deep into the nostril. There are certain disadvantages to this method:
- It is uncomfortable for patients and may contribute to “testing fatigue”
- It may not be suitable for young people or those with special needs
- It requires the use of long swabs that may be in short supply
- Samples must be collected by trained staff wearing personal protective equipment (PPE), both of which are subject to the risk of shortage
Saliva-based testing eliminates these disadvantages. It is noninvasive, suitable for all individuals, simple, and largely impervious to supply chain disruptions. Saliva samples are also stable and can be preserved for at least 20 days at 39.2°F/4°C without viral transport.
The Accuracy Issue
Given these advantages, why has saliva-based SARS-CoV-2 testing not become more widespread? A big part of the answer is concerns over test reliability, specifically the lack of data supporting saliva testing accuracy. Thus, about one year into the pandemic, the influential Infectious Diseases Society of America issued guidelines stating that “saliva as the sole sample source of COVID-19 diagnostics cannot be recommended due to a paucity of studies.”1
However, even before the pandemic began, there was growth in the research demonstrating the sensitivity and specificity of saliva testing vis-à-vis swab testing.
For example, an article published in the online version of Lancet Respiratory Medicine in April 2021 suggests that by November 2020, there were 58 studies evaluating SARS-CoV-2 detection in saliva—54 using RT-PCR, four using reverse transcription loop-mediated isothermal amplification, and three using both.2 However, because of the differences in methodologies used by the studies, detection rates were highly variable. Thus, of the RT-PCR studies:
- Most (69 percent) found greater or similar (≤10 percent difference) sensitivity between saliva and nasopharyngeal and other swab methods;
- Only 24 percent found saliva to be less sensitive than swabs; and
- Seven percent showed that results varied based on population group, stage of infection, or method.
The overall implication is that saliva-based detection is at least similar in sensitivity to swab-based detection. However, “using less robust methods can skew the sensitivities reported across studies,” the authors noted. “Importantly, saliva detected an additional 10 percent of positive individuals for whom swabs produced false negative results.”
Building the Scientific Case for Saliva SARS-CoV-2 Testing
Another 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 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-2.4
Development of Saliva SARS-CoV-2 Tests
The laboratory industry has developed saliva-based COVID-19 diagnostics products. In April 2020, less than three months into the PHE, Rutgers University secured the first EUA for a saliva COVID-19 test, the Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay test which runs on the Thermo Fisher Applied Biosystems QuantStudio 5 Real-Time PCR System.5 A month later, Rutgers’ RUCDR Infinite Biologics received an expanded EUA for a saliva assay performed on samples that users collected at home and sent to a laboratory for testing. The test, developed by RUCDR in partnership with Spectrum Solutions and Accurate Diagnostic Labs, became the first saliva assay to not require any physical interaction with a healthcare professional.
As of the date of publication, 35 different saliva-based kits have received EUA during the PHE, many for use at the point of care. That includes products from not only academic institutions but also leading commercial laboratory companies, including Thermo Fisher Scientific, PerkinElmer, BioMérieux subsidiary BioFire, Ambry Genetics, Rheonix, and NeuMoDx Molecular.
On Oct. 18, the FDA broke some new ground by issuing the first EUA for an over-the-counter saliva-based COVID molecular test to Aptitude Medical for the Metrix COVID-19 Test, a single-use test that uses real-time loop-mediated isothermal amplification (RT-LAMP) with a fluorescence reader to detect the SARS-CoV-2 virus.
SARS-CoV-2 Saliva Diagnostic Products Cleared by FDA (as of November 10, 2022)
|Company||Product & Approved Uses|
|Nanobiosym Precision Testing Services||The Nano Test for COVID-19, RT-PCR, Home Collection, Multiple Targets|
|Thermo Fisher Scientific||Amplitude Solution with TaqPath COVID-19 High-Throughput Combo Kit, RT-PCR, Multiple Targets|
|Aptitude Medical Systems Inc.||Metrix COVID-19 Test, RT-PCR, LAMP, OTC, Home Use, Screening, Multiple Targets|
|Rheonix||Rheonix COVID-19 MDx Assay, RT-PCR, Home Collection, Single Target|
|PerkinElmer||PerkinElmer New Coronavirus Nucleic Acid Detection Kit, RT-PCR, Pooling, Screening, Multiple Targets|
|MicroGEM U.S.||MicroGEM Sal6830 SARS-CoV-2 Saliva Test, RT-PCR, Multiple Targets|
|Yale School of Public Health, Department of Epidemiology of Microbial Diseases (Yale)||SalivaDirect DTC Saliva Collection Kit, DTC, Home Collection Kit, Screening|
|Yale||SalivaDirect At-Home Collection Kit, Home Collection Kit, Screening|
|Standard BioTools Inc.||Advanta Dx SARS-CoV-2 RT-PCR Assay, RT-PCR, Home Collection, Multiple Targets|
|BioFire Defense||BioFire COVID-19 Test, RT, Nested Multiplex PCR, Pooling, Multiple Targets|
|Yale||SalivaDirect for use with DTC Kits, RT-PCR, DTC, Home Collection, Screening, Pooling, Single Target|
|Yale||SalivaDirect, RT-PCR, Home Collection, Screening, Pooling, Single Target|
|University of Illinois||covidSHIELD, RT-PCR, Home Collection, Serial Screening, Pooling, Multiple Targets|
|Life Technologies Corporation (part of Thermo Fisher Scientific)||TaqPath COVID-19 Fast PCR Combo Kit 2.0, RT-PCR, Multiple Targets|
|Gravity Diagnostics||Gravity Diagnostics SARS-CoV-2 RT-PCR Assay, RT-PCR, Home Collection, Screening, Multiple Targets|
|Southern California Permanente Medical Group||Kaiser Permanente High Throughput SARS-CoV-2 Assay, RT-PCR, Home Collection, Multiple Targets|
|Mount Sinai Hospital||Mount Sinai SARS-CoV-2 Assay, RT-PCR, Home Collection, Screening, Multiple Targets|
|Infinity BiologiX||Infinity BiologiX TaqPath SARS-CoV-2 Assay, RT-PCR, Home Collection, Pooling, Multiple Targets|
|Spectrum Solutions||SDNA-1000 Saliva Collection Device|
|Ambry Genetics Laboratory||Ambry COVID-19 RT-PCR Test, RT-PCR, Home Collection, Multiple Targets|
|3B Blackbio Biotech India Ltd. (subsidiary of Kilpest India Ltd.)||TRUPCR SARS-CoV-2 Kit, RT-PCR, Multiple Targets|
|WREN Laboratories||WREN Laboratories COVID-19 PCR Test, RT-PCR, Home Collection, Screening, Multiple Targets|
|WREN Laboratories||WREN Laboratories COVID-19 PCR Test DTC, RT-PCR, DTC, Home Collection, Screening, Multiple Targets|
|WREN Laboratories||WREN Laboratories COVID-19 Saliva Test Collection Kit DTC, Home Collection Kit, DTC, Screening, Multiple Targets|
|Phosphorus Diagnostics||Phosphorus COVID-19 RT-qPCR Test, RT-PCR, Home Collection, Screening, Multiple Targets|
|Phosphorus Diagnostics||Pinpoint by Phosphorus COVID-19 Test Home Collection Kit DTC, Home Collection Kit, DTC, Screening, Multiple Targets|
|Quadrant Biosciences||Clarifi COVID-19 Test Kit, RT-PCR, Pooling, Multiple Targets|
|DxTerity Diagnostics||DxTerity SARS-CoV-2 RT PCR CE Test, RT-PCR, Home Collection, Multiple Targets|
|P23 Labs, LLC||P23 Labs TaqPath SARS-CoV-2 Assay, RT-PCR, Home Collection, Multiple Targets|
|NeuMoDx Molecular||NeuMoDx SARS-CoV-2 Assay, RT-PCR, Collection Kit, Multiple Targets|
|Express Gene LLC, DBA: Express Gene Molecular Diagnostics Laboratory||Express Gene 2019-nCoV RT-PCR Diagnostic Panel, RT-PCR, Collection Kit, Multiple Targets|
|DxTerity Diagnostics||DxTerity SARS-CoV-2 RT-PCR Test, RT-PCR, Multiple Targets|
|DNA Genotek Inc.||ORAcollect∙RNA OR-100 and ORAcollect∙RNA ORE-100 Saliva Collection Devices, Saliva Collection Device|
|DNA Genotek Inc.||OMNIgene·ORAL OM-505 and OME-505 (OMNIgene·ORAL) Saliva Collection Devices, Saliva Collection Device|
|Clinical Reference Laboratory, Inc.||CRL Rapid Response, RT-PCR, Home Collection, Single Target|
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