By Paul Nicolaus
October 19, 2021 | Several research groups and start-ups are pursuing the potential of scratch-and-sniff testing, envisioning it as a simple, cheap, and accessible tool that could help limit transmission and avoid shutdowns during the next phase of the coronavirus pandemic.
Derek Toomre, a professor in the Department of Cell Biology at the Yale School of Medicine, founded u-Smell-it, for example, to pursue the commercialization of his scratch-and-sniff test.
In a paper published in Nature Communications (DOI:10.1038/s41467-021-23315-5), he and researchers at the University of Colorado modeled the effectiveness of olfactory testing. They found that this form of monitoring could help reduce spread with regular screening and reduce risk when used at the point-of-entry for single-day events.
Olfactory screening is both scalable and inexpensive, Toomre and colleagues noted, which are “two critical factors for large population-scale testing” that differentiate this type of screening from other options, like RT-PCR or antigen testing.
In light of the estimated impact and the ability to be mass-produced, they suggested it could be a high-impact, cost-effective method for broad screening and surveillance.
What we know from testing in general, Toomre told Diagnostics World, is that it’s much more important to have high-frequency testing than high sensitivity testing. The challenge, however, is that most testing is prohibitive, either in availability or cost, to carry out on a large scale.
“We’ve known since the beginning of this outbreak that really to have testing have an impact on society and mitigate the spread of COVID, we would need to be doing about 50 million tests per day in the United States,” he said, and we’ve never made it close to that mark.
Some research has shown that it is possible to effectively move from PCR testing to antigen testing because of the quick results, Toomre pointed out, and he wanted to take that thought a step further and analyze the potential impact of olfactory testing in his study.
“The findings were rather remarkable in that a simple smell test done at a high frequency—let’s say every one to three days—would be as good as a weekly PCR test in stopping spread,” he said.
To give a sense of the big picture cost savings involved, Toomre and colleagues pointed out in their paper that testing 50 million people daily with PCR tests at the cost of $50 each amounts to $2.5 billion per day, and using $10 antigen tests daily would total $500 million per day. Meanwhile, a smell test would cost a fraction of those amounts ($12.5 million) assuming a per-test cost of $0.25.
Additional savings could be realized, too, because there is no need to implement sample collection and transport logistics.
Despite the potential upsides, the researchers acknowledged that both antigen and RT-PCR testing have been used successfully in screening and surveillance applications, and olfactory screening ought to be viewed as a complement to existing programs—not a replacement.
Test Wins XPRIZE Competition
Toomre’s u-Smell-it test was chosen as a winner of the XPRIZE rapid COVID testing competition, which asked entrants to develop fast, frequent, cheap, and easy-to-use solutions.
“They were looking for a test that would be less than the cost of a latte,” he explained, and “we know ours could be less than a dollar. They were looking for tests that you can get done in half an hour, and we can do our test in about one minute.” The competition also searched for solutions that could be manufactured and deployed at scale. “A large commercial printer, we believe, could manufacture 50 to 100 million tests per day.”
Because many with COVID-19 experience diminished or no sense of smell, and because people often do not notice this symptom on their own, the thought is that an objective screening tool could be helpful. It is a “less accurate, less sensitive test,” Toomre explained, but it can be done both “cheaply and easily.”
The only items required to use this form of screening are the u-Smell-it smell cards and a phone or tablet with an internet connection. After downloading the app, users open it and scan the QR code on the card. From there, it’s a matter of scratching or rubbing box 1, smelling it, choosing the best option in the app, and repeating that process for all five boxes.
The u-Smell-it test takes less than a minute to complete, and the app automatically scores the test results, which are provided immediately. It was designed to be child-friendly, using scents that children can identify and providing pictures to help make selections without having to read text.
Those who do not pass the test see a red light and are told to take another. If two tests are failed, they are encouraged to contact a medical professional. He emphasized that this is not a diagnostic test but rather a screening tool that can help indicate a loss of smell.
The test has already been sold in Germany, and Toomre hopes it will soon be made available in other parts of the world, including the United States. Application for Emergency Use Authorization (EUA) with the Food and Drug Administration (FDA) was submitted in October 2020.
“I think in the US, you could see it really being useful in a scenario where you want to test a lot of people quickly,” he explained, if the results don’t have to be perfect but an extra level of safety is desired in settings such as schools, restaurants, sports stadiums, and concert venues.
Beyond that, Toomre said there is a need for testing in many parts of the world—especially in areas with low levels of vaccination or an inability to afford more costly forms of testing.
Personal Experience Sparks Start-Up
Sarah Davis, a family medicine physician in Dallas, Texas, is another who has worked to bring the thought of a smell test to life in response to the pandemic.
The idea struck her after her daughter contracted COVID in the summer of 2020 while working as a camp counselor. Davis said symptoms included a bit of fatigue and a short-lived fever, but most notably there was a complete loss of sense of smell.
“I just thought that was very interesting,” she told Diagnostics World, “because in all the other cold viruses that I’ve seen my entire career, I’ve never seen something like that—that was so unique and isn’t present with any other virus.”
At that time, she was already thinking that this was not going to go away completely, and she may be seeing it for the rest of her career. “How am I going to distinguish that?” she wondered.
The solution she came up with is a scent card from SAFER Diagnostics, the start-up she founded. A research letter published in JAMA Otolaryngology-Head & Neck Surgery (DOI: 10.1001/jamaoto.2021.1456) detailed the early promise shown by this tool.
Because subjective olfactory assessments significantly underreport compared with objective testing, a method of assessing sense of smell that is quick, inexpensive, and sensitive could be helpful for early diagnosis and the prevention of spread, Davis and coauthors explained.
“Olfactory dysfunction (OD) is one of the earliest and strongest predictors of COVID-19 infection, and thus is promising as a disease screening tool,” they wrote.
In their pilot study, the researchers looked at the performance of an olfactory test that could be used as part of an initial screening for COVID-19 in adults who have an unknown disease status.
The SAFER scent card includes a single scent in a scratch-and-sniff label. Each study participant identified the odor from a slate of eight options (lemon, grape, floral, blueberry, banana, mint, unsure, or no scent). Answers were processed using a QR code, and an incorrect selection was classified as OD.
The study included 163 healthy adults from a college campus COVID-19 screening site who were screened for OD using the scent card and then by PCR testing using nasopharyngeal swabs. Of the participants who tested PCR-positive for COVID-19, 75% (12 out of 16) failed olfactory screening. Of those who tested PCR-negative, 4.8% (7 out of 147) failed the screening.
Ideally, the researchers pointed out, a screening test prioritizes high sensitivity with the potential for lower specificity. Using a single scent might demonstrate lower sensitivity in exchange for speed. The number of screening scents needed to reach a high sensitivity while remaining quick and practical could be a focus for future research.
The study’s limitations included its small sample size, low percentage of PCR test-positive participants, and the recruitment of participants from just one institution.
“Future studies with a larger sample size and a heterogeneous population may better account for other OD risk factors and optimize sensitivity using a combination of OD testing with other symptoms for screening COVID-19,” they concluded.
SAFER Scent Card Goes Live
“We’ve already contracted with a lot of different distributors, who are going to be kind of boots-on-the-ground and going out and demonstrating it to people and selling it in large quantities,” said Davis. The product is also available through the company’s website.
According to Davis, because the scent card is an olfactory test and not a COVID test, it does not require FDA approval. “There’s nothing in this that is actually checking for COVID,” she said. “It is checking for lack of sense of smell, which is correlated with COVID.”
Of the tool’s advantages, she said, it is cheap, fast, easy to use, and does not require anything more than a single smartphone. The screening process only takes about 20 seconds to complete.
The SAFER card system works with any mobile phone (or other device with a camera capable of scanning a QR code and visiting a website). Users point the device’s camera application at the QR code on the SAFER card, and the system then provides step-by-step instructions.
The company says its scent card system is “one of the fastest, most practical tools to help businesses, organizations, and campuses identify who should be further tested for COVID-19.” It is intended for regular use in settings where people come together but is not intended to be relied upon as a substitute for FDA-approved COVID-19 testing.
Davis noted that it could be used worldwide, including settings where not everyone has a smartphone or tablet. One individual could help screen 100 people, for example, using a single device.
“We don’t necessarily have to test everybody,” she explained. Screening can help determine who needs to be tested, saving money and time, and hopefully decreasing infections.
“We can make hundreds of millions of these that are very inexpensive—so much so that you can have people do this over and over again,” she said. And some of the limitations regarding accuracy can be overcome, at least to an extent, by frequent use.
But some caveats come into play, too.
“The biggest one is not everybody who gets COVID loses their sense of smell,” she pointed out. For example, in their pilot study, one out of every four people who had COVID still passed this screen. “You don’t want to use it as your only measure of whether or not somebody has COVID because you are going to miss some.”
On the other hand, some people who don’t have COVID will still fail the screen. “Just like any test, you’re always going to have those people that are on the outside margins of it,” she explained. And that specificity could be lower in certain groups.
If somebody had COVID and recovered from it several months ago, for example, they are not contagious anymore but may still fail the SAFER screen. Others may not have a good sense of smell in general. Because of this, she said any organization would need to have some sort of opt-out for those who aren’t necessarily a good fit for this type of test.
NIH Award Supports Smell Test Endeavor
Yet another group is focused on examining two different scratch-and-sniff smell tests.
Researchers at the University of Florida, Penn State, and Arizona State University received $912,000 from the National Institutes of Health (NIH) and are working toward the development of tests to help flag new cases and provide a warning of emerging hotspots.
Study participants are asked to use the two tests to determine which is a better predictor of a COVID diagnosis. One asks users to identify odors like onions, smoke, and chocolate. The other is intended to reveal a person’s sensitivity to different concentrations of the same odor.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.