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Ask an Infectious Disease Expert: Which COVID-19 Rapid Tests Are Most Accurate?

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Makeda Robinson, MD, PhD, is an infectious disease specialist currently studying virus-host interactions in emerging viruses at Stanford University. Each week, Dr. Robinson breaks down complicated COVID-19 topics and addresses pressing public health concerns.

With massive testing shortages, ineffective tests, and an inability to implement widespread testing strategies, the U.S. has been plagued by testing-related issues since the start of this pandemic. However, as technology catches up with the evolving information surrounding SARS-CoV-2, scientists are beginning to develop innovative, rapid, and accurate tests that can help curb the spread of COVID-19.

One of these tests, SalivaDirect, was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) in August and has the potential to change the infrastructure of U.S. testing procedures. How does this test work? How does it stack up compared to other tests that have received EUA? Dr. Robinson spoke with Verywell Health about the latest testing options.

Verywell Health: How does SalivaDirect work and why has it gotten so much recent attention? 

Dr. Robinson: SalivaDirect requires users to collect their own saliva in a sterile container where it is then sent to a lab for processing. (Editor's note: According to the FDA, the sample must be be collected under the supervision of a physician.) One of the reasons this test has gotten so much attention is because it’s quick, cheap, and easy.

To make this test more widely available, researchers at the Yale School of Public Health tested SalivaDirect using multiple machines and found that their protocol did not need a specific vendor’s machine to work efficiently. This means that labs interested in using this test would likely not need to purchase any special equipment to run this test. This is an important issue when thinking about supply chain bottlenecks.

These innovative tweaks lead to cost reduction and faster turnaround times. With SalivaDirect, we’re looking at less than 24 hours for results and a cost per test of less than $10 to the public. Cost is a major issue when you're thinking about scaling up testing, especially in middle- or lower-income countries that may want to do broader population testing. As we look to ramp up diagnostic testing to include people without symptoms, SalivaDirect could be a great option. 

Verywell Health: How were researchers able to make a faster, cheaper test? What's different about its technology?

Dr. Robinson: The researchers who created the test made two major modifications to standard PCR tests.

First, they did not include specific compounds that are commonly used during specimen collection, which significantly reduced the cost of making SalivaDirect. These nucleic acid preservatives are typically added to the collection container to improve the RNA integrity of your sample. With SalivaDirect, the researchers evaluated whether the preservatives were necessary when testing for SARS-CoV-2, and they did not find any significant differences in the testing accuracy when they were excluded. In fact, they found an improvement in detection after seven days at warm temperatures.

The second thing they modified—which can have a larger influence on the testing outcome—is the RNA extraction step. This step is used to concentrate and extract RNA from the sample specimens to improve the accuracy of the test. The majority of our current SARS-CoV-2 PCR diagnostic tests use this step, which requires special nucleic acid extraction kits. Unfortunately, we have had a shortage of these kits throughout the pandemic. The SalivaDirect protocol cuts out the RNA extraction step.

In order to eliminate this step but maintain accuracy, the scientists that created SalivaDirect substituted the RNA extraction with the addition of an enzyme, Proteinase K. Proteinase K can inactivate proteins that can degrade the RNA within the samples.

Verywell Health: How does SalivaDirect compare to other diagnostic saliva tests for SARS-CoV-2?

Dr. Robinson: I think, in part, SalivaDirect stands out from other diagnostic tests through its improvement on cost and accessibility. In April, the FDA issued its first EUA for a saliva test created by Rutgers Clinical Genomics Laboratory. This is currently commercially available, but it retails for $150, so there is a large price difference between this and SalivaDirect. [The Rutgers] test, however, falls more in line with traditional PCR tests, because physicians perform an RNA extraction step.

Verywell Health: How does SalivaDirect compare to standard nasopharyngeal swabs? 

Dr. Robinson: An important difference is that you can collect a saliva sample yourself. During a nasopharyngeal swab, you may experience increased coughing and sneezing, putting the healthcare worker administering the test at risk.

What Is a Nasopharyngeal Swab?

A nasopharyngeal swab takes a sample from deep inside the nose, reaching the back of the throat.

Saliva tests may also be a bit more consistent. The results of a nasopharyngeal swab test can depend on the person obtaining the specimen. The human factor can play a major role if the swab is not placed deep enough to obtain a sufficient sample.  

Also, many people find it uncomfortable to get a swab test. So a saliva test might be beneficial if more people are willing to get tested due to ease and comfort.

Verywell Health: Do you think that saliva tests might replace nasopharyngeal swab tests? 

Dr. Robinson: I think both tests have a place in the healthcare industry.

Saliva tests may be more useful in the outpatient setting with people who have mild symptoms. But patients who are already hospitalized may have more difficulty producing enough saliva. Issues such as dry mouth and increased mucus or blood production may inhibit the testing procedure.

Sensitivity vs. Specificity

  • Sensitivity is the percentage of people who are infected who actually show a positive test result.
  • Specificity is the percentage of people who are not infected who actually show a negative test result.

Verywell Health: What are the sensitivity and specificity levels of SalivaDirect? 

Dr. Robinson: The SalivaDirect test does appear to have a slight reduction in sensitivity compared to the standard PCR test because it skips that RNA extraction step. However, this was to be expected. This reduction in sensitivity will lead to more false negatives. Three out of 41 positive patients will be missed by SalivaDirect.

To determine specificity, researchers looked at whether this testing strategy would lead to any cross-reactivity for flu. Would this test lead to false positive results in people with who had the flu but did not have SARS-CoV-2? They tested samples from the preceding two year’s flu strains and found that their test did not cross-react with those flu strains, meaning it is highly specific for SARS-CoV-2. 

Verywell Health: Which other approved diagnostic tests do you think could be game-changers?

Dr. Robinson: The llumina (COVIDSeq) is another testing approach that has its own unique benefits. It can batch up to 3,000 samples at once, producing results in 24 hours. [Researchers] are reporting a sensitivity of 98% and specificity of 97%.

This test uses nasopharyngeal and oropharyngeal swabs, not saliva. However, it stands apart from other tests as it allows researchers to sequence the virus and can give insights about transmission chains and mutation rates. As the SARS-CoV-2 virus spends more time interacting with the human immune system, it will try to find ways to evade our defenses by mutating. These mutations are something that we need to keep a close eye on when thinking about vaccines and therapeutics and can be monitored by using sequencing technology.

One limitation of this testing strategy is that issues may arise due to the need for specific equipment from a specific vendor, which could lead to supply chain issues. 

The DETECTR test is another diagnostic testing approach with EUA from the FDA. It uses multiple advanced technologies to reduce the turnaround time to under one hour, which could be truly transformative.

Verywell Health: How can the abundance and accessibility of rapid tests help inform public health policies and containment efforts?

Dr. Robinson: I believe that we currently have the necessary tools to contain this virus. Public health measures through the individual efforts of mask usage and social distancing as well as widespread diagnostic testing and contact tracing have shown their power to protect our communities from the transmission of COVID-19.

We’ve seen that these measures can make a huge difference in other countries like South Korea and Taiwan, who focused very early on containment efforts and have kept their case numbers relatively low. At-home and rapid tests can aid us in our efforts, and they are another potential tool in the toolbox for reopening in a safe way.

For example, as some companies are beginning to think through the logistics of having a subset of employees return to the office, having rapid, at-home testing protocols could allow us to begin to do that in a much safer way. Ideally, we would build upon the trio of hand hygiene, masks, and social distancing, adding on rapid at-home testing and more advanced tech-driven contact tracing. These approaches could also be applied to the school setting. 

Given the extraordinary impact of this pandemic, I feel as though there is a sense of helplessness at times, but I believe this is a time to invest in our communities and begin to open our eyes to the need for fundamental investments in public health infrastructure. We are no safer from the next unnamed virus than we were at the start of 2020. 

Verywell Health: A lot of these inexpensive rapid tests have been shown to have lower sensitivity. Do you think it's more important to have highly-accurate tests or accessible tests?

Dr. Robinson: A lot of this depends on what you’re trying to accomplish with diagnostic tests. We use diagnostic tests to answer multiple questions, including whether someone has an acute infection, if they’ve recovered, or if someone has an asymptomatic infection.

We also use these tests to get population-wide data to better understand who has already been infected. So depending on what question you're asking, you may want an extraordinarily sensitive test, or you may want a test with better scalability, meaning one that's cheap and easy to use that you can administer to larger populations. I wouldn't say one is more important than the other, but that the type of test should be tailored to the question you’re trying to answer. 

I do think that rapid at-home tests can be useful at illuminating the black box of those who are “unknowingly infected” or asymptomatic cases. As we now have good accurate standard PCR tests, I think the focus should be on further validating these faster, cheaper tests and finding ways to implement them in a streamlined fashion.  

Verywell Health: Are there tests than can simultaneously detect both COVID-19 and influenza?

Dr. Robinson: Yes. In July, the FDA issued a EUA for the CDC Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay test. This test is an RT-PCR assay that is able to differentiate between SARS-CoV-2 and two types of influenzas: influenza A virus and influenza B virus. 

Developing these kinds of tests prior to the flu season is incredibly important. As we move further into fall and begin to learn how school re-openings and a return to office work affect the pandemic, tests like this will help inform effective treatment regimens. These tests will also help us understand overlapping symptomatology and how common co-infections may be.

Verywell Health: What do you think the next step in testing should be?

Dr. Robinson: I think improving access to testing facilities and shortening the turnaround time are both crucial next steps in our approach to SARS-CoV-2. 

We need to think strategically about who and where we are testing and create diagnostic testing centers in places that have been hard hit by the virus. Further educating communities about the testing process and encouraging people who may not be at high risk themselves but interact with high-risk populations, such as those living in multigenerational homes, could make a deep and broad impact on controlling the spread of the virus.

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