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YSPH Research Scientist Anne Wyllie Discusses Success of SalivaDirect Testing Protocol

July 25, 2022

On July 28 and 29, researchers, industry professionals, and public health leaders from around the world will gather in Chicago, Illinois for the first annual conference on saliva-based testing hosted by the SalivaDirect Initiative of the Yale School of Public Health. During the two-day event, attendees will discuss lessons learned about saliva-based testing during COVID-19 and explore potential new roles for the technology in improving public health and future global emergency response.

Developed in 2020 during the early days of the COVID-19 pandemic, SalivaDirect is an open-source PCR test that is less costly, less time-consuming, and more patient-friendly than tests requiring a nasal swab. Given the protocol’s proven sensitivity and reliability, the U.S. Food and Drug Administration granted SalivaDirect an Emergency Use Authorization (EUA) in August 2020. Since then, the Yale School of Public Health has designated 184 laboratories nationwide to use SalivaDirect and more than 7 million tests have been performed to date.

Yale School of Public Health Research Scientist Anne Wyllie, principal investigator for the SalivaDirect Initiative, recently discussed the upcoming conference, the success of SalivaDirect, and its potential future applications.

What motivated you to host the upcoming conference about saliva-based testing?

AW: Our clinical laboratory partners in more than 40 states and territories motivate everything we do at the SalivaDirect Initiative. Their collective efforts during the last two years represent a tremendous achievement in pandemic response. I’m honored to call them colleagues and inspired by their dedication. It’s been an incredible journey. This conference will showcase the one-of-a-kind public health alliance into which SalivaDirect has evolved. We’re especially inspired by the intention of so many laboratory leaders to align with SalivaDirect’s goal of increasing access to equitable testing for all communities. This conference is one of the many ways we continue to advance that mission and foster additional scientific collaboration.

What do you hope to achieve at the conference?

AW: Our aim is to 1) acknowledge and share COVID-19 lessons learned up to this point in the pandemic, 2) begin formalizing the SalivaDirect laboratory network as a pandemic-ready emergency response mechanism, and 3) cultivate interest for research that could further unlock the power of saliva as a diagnostic methodology. Also, we’re eager to learn how best to continue supporting our SalivaDirect laboratory partners as public health champions both in their contributions to research and to healthcare in their communities.

What future applications does the SalivaDirect Initiative plan to develop?

AW: COVID-19 demonstrated the global necessity for labs to have tests that are flexible, easy to implement, and readily scalable with minimal capital investment, and multiple supply lines. To achieve the sustained high patient compliance needed to mitigate widespread disease transmission, ideal tests should be non-invasive, self-administered, quick, and affordable. Saliva-based tests have offered these benefits and more during the COVID-19 pandemic.

Moving into new phases of the COVID-19 pandemic, our research at SalivaDirect continues to evolve. We are monitoring emerging variants to ensure our assay continues to accurately identify positive cases. Working with the FDA to transition our EUA to a full regulatory authorization known as a 510(k) is also a priority. We have also submitted for regulatory approval (CE Mark) in the European Union.

We are currently developing new saliva-based tests for influenza A/B and respiratory syncytial virus (RSV). We’ll add these targets to our current assay to create a three-in-one or multiplex test. This will allow labs to test a single specimen for all three viruses at the same time. We also are identifying other diseases and conditions for which saliva-based tests could improve diagnosis and access to patient care.

What were the most important lessons you learned in developing SalivaDirect and sharing it with the world?

AW: To start, we appreciate the immense potential of open science to produce rapid innovation to support pandemic response. Using this strategy to launch SalivaDirect nationally taught us how to maximize the scarce resources of a single lab for the benefit of many labs and patients. COVID-19 showed the importance of leveraging existing national laboratory infrastructure. We designed SalivaDirect to be used with low-cost reagents, collection kits, and PCR machines that most high-complexity labs have readily available. We included materials from multiple manufacturers in the EUA, allowing for substitutions to guard against supply chain shortages or delays.

Even more, I appreciate the miracles that our small and mighty team at Yale continues to generate in fulfillment of our mission. From the start, we had very limited resources, which is still the case. However, in the spirit of collaboration so many individuals and organizations, here at Yale and around the world, have contributed in much the way crowdsourcing works. It’s incredible to see how much we have achieved and continue to create.

The SalivaDirect Initiative’s mission emphasizes the importance of equitable access to testing. Can you elaborate on how SalivaDirect is helping make testing more equitable?

AW: As public health specialists, we are driven to develop solutions that deliver equitable access to care. Many communities struggled to launch wide-scale testing at the start of the pandemic because they didn’t have the resources – tests were too expensive, especially for our most vulnerable communities. Unfortunately, this issue is still prevalent today. Our mission at SalivaDirect is to drive down testing costs for labs so savings can be passed on to the communities they serve. We accomplished this by launching our test as an open-source protocol free of charge. We validated numerous low-cost reagents and many PCR machines for use with the test and eliminated one of the costliest and most time-consuming steps of the PCR testing process — RNA extraction.

With SalivaDirect, labs use fewer resources (staff, time, budget) and many significantly increase the number of tests they can process in a day. Importantly, saliva specimens can be collected without the need for highly skilled health care workers - people can simply collect their own saliva at either a testing center or their homes. As a result, health care workers can remain active in direct patient care and less personal protective equipment is needed. All of this is to say, SalivaDirect is a lower-cost, high-quality PCR testing option. Reducing the costs associated with molecular testing stretches laboratory resources and federal and state budgets, as well as lowers the cost to patients. Together these factors can add up to more equitable access to testing for patients.

Did you ever imagine the SalivaDirect protocol would be so widely used when you first conceived the idea of applying it to COVID-19?

AW: Yes and no. I’ve been researching saliva as a sample type for infectious disease surveillance for more than a decade. At the start of the pandemic, I recognized that it could be a public health game changer for communities. When developing the SalivaDirect COVID-19 protocol, we specifically intended to address as many testing challenges as possible.

To make it easier for labs to start running the protocol, we developed three different ways to conduct the test. To minimize supply chain pressure and leverage the availability of existing resources, the test includes more than a dozen reagents and 26 PCR machines. That’s a lot of variables. And, I’m pleased to report that during these last two years, the SalivaDirect network of more than 180 independent labs performed more than 7 million tests with far fewer problems reported as compared to nasal swab tests.

I am really pleased with the test’s reliability. The overall number of tests performed is also amazing, and we strive to increase it. With dwindling government financial support for testing in general, the low cost of running SalivaDirect tests makes it even more useful for laboratories, state health departments, school systems, employers, and communities to provide molecular testing.

And while you didn’t ask, I will also add - to keep our children in school, our workforce employed, and our supply chain vibrant, COVID-19 testing continues to be an important element of pandemic management. Our communities must remain vigilant against SARS-CoV-2. I’m confident the SalivaDirect Initiative will continue supporting these efforts by providing equitably testing options.

Submitted by Colin Poitras on July 23, 2022