Thursday, 28 March, 2024
HomeCoronavirusSaliva-based COVID-19 diagnostic test given FDA emergency use authorisation

Saliva-based COVID-19 diagnostic test given FDA emergency use authorisation

A saliva-based laboratory diagnostic test developed by researchers at the Yale School of Public Health to determine whether someone is infected with the novel coronavirus has been granted an emergency use authorisation by the US Food and Drug Administration (FDA).

The method, called SalivaDirect, is being further validated as a test for asymptomatic individuals through a programme that tests players and staff from the National Basketball Association (NBA). SalivaDirect is simpler, less expensive, and less invasive than the traditional method for such testing, known as nasopharyngeal (NP) swabbing. Results so far have found that SalivaDirect is highly sensitive and yields similar outcomes as NP swabbing.

With the FDA’s emergency use authorisation, the testing method is immediately available to other diagnostic laboratories that want to start using the new test, which can be scaled up quickly for use across the nation – and, perhaps, beyond – in the coming weeks, the researchers said.

A key component of SalivaDirect, they note, is that the method has been validated with reagents and instruments from multiple vendors. This flexibility enables continued testing if some vendors encounter supply chain issues, as experienced early in the pandemic.
“This is a huge step forward to make testing more accessible,” said Chantal Vogels, a Yale postdoctoral fellow, who led the laboratory development and validation along with Doug Brackney, an adjunct assistant clinical professor. “This started off as an idea in our lab soon after we found saliva to be a promising sample type of the detection of SARS-CoV-2, and now it has the potential to be used on a large scale to help protect public health. We are delighted to make this contribution to the fight against coronavirus.”

Development of SalivaDirect as a means of rapidly expanding SARS-CoV-2 testing was spearheaded this spring by Nathan Grubaugh and Anne Wyllie, assistant professor and associate research scientist, respectively, at Yale School of Public Health. After finding saliva to be a promising sample type for SARS-CoV-2 detection, they wanted to improve the method further.

“With saliva being quick and easy to collect, we realized it could be a game-changer in COVID-19 diagnostics,” said Wyllie. With testing urgently needed, the Yale team was determined to decrease both testing times and costs, to make testing widely accessible.

“Wide-spread testing is critical for our control efforts. We simplified the test so that it only costs a couple of dollars for reagents, and we expect that labs will only charge about $10 per sample. If cheap alternatives like SalivaDirect can be implemented across the country, we may finally get a handle on this pandemic, even before a vaccine,” said Grubaugh.

One of the team’s goals was to eliminate the expensive saliva collection tubes that other companies use to preserve the virus for detection.

In a separate study led by Wyllie and the team at the Yale School of Public Health, they found that SARS-CoV-2 is stable in saliva for prolonged periods at warm temperatures, and that preservatives or specialized tubes are not necessary for collection of saliva.

The Jackson Laboratory for Genomic Medicine in Farmington, Connecticut, will partner with Yale to explore how to implement the test for a broader audience. The laboratory already analyses patient samples for an RNA signature unique to that of SARS-CoV-2, the virus that causes COVID-19.

“We must continue to invent and implement new ways to conduct SARS-CoV-2 testing faster, more economically and with greater accessibility, while maintaining acceptable test accuracy,” said Charles Lee, the laboratory’s director. “This method is an important next step toward this goal.”

Grubaugh and Wyllie said that they are not seeking to commercialise the method. Rather, they want the simplified testing method to help those most in need. Testing for SARS-CoV-2 has been a major stumbling block in the fight against the pandemic, with long delays and shortages of testing.

Some experts have said that up to 4m tests are needed per day; SalivaDirect provides one pathway toward that goal, the researchers said. “Using SalivaDirect, our lab can double our testing capacity,” said Professor Chen Liu, chair of Yale Pathology, who oversaw the clinical validation of the study.

“Dr Liu and Yale Pathology Laboratory were instrumental in our application. We look forward to continuing to partner with them,” said Grubaugh.

Liu will start offering SalivaDirect as a testing option in their CLIA-certified clinical laboratory in the coming days.

The related research was funded by the NBA, National Basketball Players Association, and a Fast Grant from the Emergent Ventures at the Mercatus Centre, George Mason University.

Abstract 1 (not peer reviewed)
Current bottlenecks for improving accessibility and scalability of SARS-CoV-2 testing include diagnostic assay costs, complexity, and supply chain shortages. To resolve these issues, we developed SalivaDirect. The critical component of our approach is to use saliva instead of respiratory swabs, which enables non-invasive frequent sampling and reduces the need for trained healthcare professionals during collection. Furthermore, we simplified our diagnostic test by (1) not requiring nucleic acid preservatives at sample collection, (2) replacing nucleic acid extraction with a simple proteinase K and heat treatment step, and (3) testing specimens with a dualplex quantitative reverse transcription PCR (RT-qPCR) assay. We validated SalivaDirect with reagents and instruments from multiple vendors to minimize the risk for supply chain issues. Regardless of our tested combination of reagents and instruments from different vendors, we found that SalivaDirect is highly sensitive with a limit of detection of 6-12 SARS-CoV-2 copies/μL. When comparing paired nasopharyngeal swabs and saliva specimens using the authorized ThermoFisher Scientific TaqPath COVID-19 combo kit and our SalivaDirect protocol, we found high agreement in testing outcomes (>94%). Being flexible and inexpensive ($1.29-$4.37/sample), SalivaDirect is a viable and accessible option to help alleviate SARS-CoV-2 testing demands. We submitted SalivaDirect as a laboratory developed test to the US Food and Drug Administration for Emergency Use Authorization on July 14th, 2020, and current details can be found on our website (covidtrackerct.com/about-salivadirect/).

Authors
Chantal BF Vogels, Doug Brackney, Jianhui Wang, Chaney C Kalinich, Isabel Ott, Eriko Kudo, Peiwen Lu, Arvind Venkataraman, Maria Tokuyama, Adam J Moore, M. Catherine Muenker, Arnau Casanovas-Massana, John Fournier, Santos Bermejo, Melissa Campbell, Rupak Datta, Allison Nelson, Yale IMPACT Research Team, Charles Dela Cruz, Shelli Farhadian, Albert Ko, Akiko Iwasaki, Pei Hui, Chen Liu, Anne L Wyllie, Nathan Grubaugh

Abstract 2 (not peer reviewed)
Most currently approved strategies for the collection of saliva for COVID-19 diagnostics require specialized tubes containing buffers promoted for the stabilization of SARS-CoV-2 RNA and virus inactivation. Yet many of these are expensive, in limited supply, and not necessarily validated specifically for viral RNA. While saliva is a promising sample type as it can be reliably self-collected for the sensitive detection of SARS-CoV-2, the expense and availability of these collection tubes are prohibitive to mass testing efforts. Therefore, we investigated the stability of SARS-CoV-2 RNA and infectious virus detection from saliva without supplementation. We tested RNA stability over extended periods of time (2-25 days) and at temperatures representing at-home storage and elevated temperatures which might be experienced when cold chain transport may be unavailable. We found SARS-CoV-2 RNA in saliva from infected individuals is stable at 4°C, room temperature (~19°C), and 30°C for prolonged periods and found limited evidence for viral replication in saliva. This work demonstrates that expensive saliva collection options involving RNA stabilization and virus inactivation buffers are not always needed, permitting the use of cheaper collection options. Affordable testing methods are urgently needed to meet current testing demands and for continued surveillance in reopening strategies.

Authors
Isabel M Ott, Madison S Strine, Anne E Watkins, Maikel Boot, Chaney C Kalinich, Christina A Harden, Chantal BF Vogels, Arnau Casanovas-Massana, Adam J Moore, M. Catherine Muenker, Maura Nakahata, Maria Tokuyama, Allison Nelson, John Fournier, Santos Bermejo, Melissa Campbell, Rupak Datta, the Yale IMPACT Research team, Charles S Dela Cruz, Shelli F Farhadian, Albert I Ko, Akiko Iwasaki, Nathan D Grubaugh, Craig B Wilen, Anne Louise Wyllie

 

[link url="https://news.yale.edu/2020/08/15/yales-rapid-covid-19-saliva-test-receives-fda-emergency-use-authorization?utm_campaign=KHN%3A%20Daily%20Health%20Policy%20Report&utm_medium=email&_hsmi=93361266&_hsenc=p2ANqtz-9M8RDoSw780uE-Fl9NvC91FvxyDPsKh_asEd7hraBV8Pj9we-e9Edbe90bnbodwMJ0KiczHbfg37ZinOn4doUc0ZcwCg&utm_content=93361266&utm_source=hs_email"]Yale University material[/link]

 

[link url="https://www.medrxiv.org/content/10.1101/2020.08.03.20167791v1"]medRxiv abstract 1 (not peer reviewed)[/link]

 

[link url="https://www.medrxiv.org/content/10.1101/2020.08.03.20165233v1"]medRxiv abstract 2 (not peer reviewed)[/link]

MedicalBrief — our free weekly e-newsletter

We'd appreciate as much information as possible, however only an email address is required.