Over-the-counter COVID-19 tests make big promises. Do they deliver?

Ashley Brigham was at a testing site a few weeks ago, weighing her two options.

Brigham, who had been exposed to someone with COVID-19 at an April fundraiser in Worcester, Massachusetts, could get a traditional molecular diagnostic test that might take hours, if not days, to deliver a result. Or she could try something new as part of a community testing project: an at-home, over-the-counter (OTC) test that would give her an answer in just a few minutes.

The 32-year-old insurance adjuster had been exposed to COVID-19 a couple of times before and had navigated isolation in a small house with two roommates, one with health issues. She chose the faster OTC test.

“I like the at-home idea. You get an immediate result,” Brigham says. “You don’t have to worry about, ‘Oh, I might have it, I might not have it.’ You [don’t] have to sit around for 3 days waiting, like not even going out in public, worried that if I do have it, then I’ll be exposing other people.”

The conundrum of how humans behave while waiting for test results has been a major driver of the development of at-home COVID-19 testing. Of the 370 COVID-19 diagnostic tests that the US Food and Drug Administration has authorized for emergency use in the US, there are dozens you can take at home. Some of these at-home tests require a prescription or telehealth monitoring. With others, you take a sample and mail it in for results. And of those at-home tests, six are recently authorized rapid COVID-19 diagnostics that give results within a few minutes. These tests are sold OTC, much like pregnancy tests or blood glucose tests.

These OTC COVID-19 tests come from diagnostic giants like Abbott Laboratories and newer companies like Lucira Health. The technology behind the assays ranges from novel to tried and true, optimized for home use. These are tests that people can or will be able to order online, or buy at the drugstore, and take at home with the aid of videos, smartphone apps, and a little diligence. The companies who make them say businesses and schools can use them at their front doors when people start flooding offices andclassrooms.

COVID-19 testing will continue to be important, experts say, even as more people get vaccinated. SARS-CoV-2, the virus that causes COVID-19, is mutating (see page 18). It’s likely to stick around, becoming another in a slew of respiratory viruses that cause similar symptoms but are treated in substantially different ways. At-home tests may be a realization of technological advances in molecular biology, biochemistry, and engineering, but they are also a response to a critical consumer demand, says Bruce Tromberg, director of the US National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering, which has been funding the development of rapid COVID-19 tests through its Rapid Acceleration of Diagnostics (RADx) Tech initiative.

“Fundamentally, it’s about access to convenience,” he says.

Tromberg looks at rapid testing as a way not just to diagnose but to prevent disease. To do that, he says, the US needs to be performing millions of tests per day. So the tests have to be simple and reliable. The RADx program is funding community testing efforts in North Carolina and Tennessee using Quidel’s OTC kit, as well as testing programs like the one Brigham participated in through the University of Massachusetts Medical School.

“If you’re on a screening-and-surveillance effort and you want to keep a large population safe and break that uninterrupted chain of transmission of the virus, then you want to have something that’s very accessible, inexpensive, deployable, that people can use like brushing teeth,” Tromberg says.

Like brushing teeth. After hearing from Tromberg and others about OTC tests, I decided to take them myself. If the expectation is that we can do these at home, without medical help, I wanted to see how easy they were to perform. To get FDA authorization, companies must show that the tests can be done by average people. But how things go during clinical validation might be different from how they go in houses or the front doors of a busy school.

I tried what was available by late April: two molecular tests, from Lucira and Cue Health, and three antigen tests, from Abbott, Ellume, and Quidel. (Abbott has two technologically similar OTC tests available, but one requires telehealth. I skipped that one.)

I compared the five OTC rapid tests with a lab-performed molecular test, all taken on the same day. Having already had COVID-19 and been vaccinated, I assumed all the tests would be negative. But with many diagnostics experts’ concerns about the accuracy of some types of rapid tests and with the slight possibility that I might have encountered a variant in my day-to-day life, I wanted to compare the at-home tests with a lab test, which many experts consider more accurate, even if it took a little longer to get the results.

Critiquing my nasal swab technique was my friend Britt Radomski, who, as a licensed pharmacist in the Pittsburgh area, has helped countless people take COVID-19 tests. While she wasn’t coaching me, as she does customers at her store, she watched remotely. She was looking out for any mistakes that might affect the outcome of my test.

By the time I finished the last test, my nose was a little sore. Yet, despite my general clumsiness and occasional confusion, the tests were relatively simple. For the most part, directions were readable, watchable, and understandable, and the results fast and easy to read.

But results are really only the beginning.

Because of sensitivity issues, some of these OTC tests are designed to be taken more than once, just in case your viral load is below detection the first time. The tests typically aren’t cheap, either, meaning that in some communities, the people at highest risk of infection won’t have easy access to them. In addition, outside the organized testing projects like the one Brigham was involved in, most of these OTC tests are not tied to doctors, public health departments, or any measure of accountability other than the entity requiring the test, such as an employer or a sporting venue.

And while leaders at the companies who spoke with me about their OTC tests say they believe anybody who would take an at-home test would most likely sequester themselves if they tested positive, Shobita Parthasarathy, a science and public policy expert at the University of Michigan, says human behavior is hardly ever so cut and dried.

The US still has no broad COVID-19 testing strategy, Parthasarathy says. US companies keep churning out tests and pushing through new technologies to deliver the tests faster and more simply, but we don’t have a meaningful way to manage the results of those tests, she says. OTC COVID-19 diagnostics exemplify this.

“We can’t tech our way out of this, and we keep trying to find ways to tech our way out,” Parthasarathy says.

She points out that if you are the person responsible for feeding your family, if your job doesn’t offer sick leave, or if you have no child care and your kid is the one who tests positive, however thoughtful and conscientious a person you are, you may not be able to sequester yourself.

“By and large, certainly in the US context, you don’t get a lot of support to stay at home,” she says.

With that in mind, I laid out the kits on my kitchen counter, called Radomski via Zoom, and starting sticking swabs up my nose.

OTC tests come in two flavors: antigen and molecular. Antigen tests detect small pieces of viral proteins that are either on the surface of infected cells or in bodily fluids. These small pieces are called antigens, and in the course of a disease like COVID-19, they are what the immune system recognizes as signs of infection. Molecular tests detect the virus’s genetic instructions, the nucleic acids that allow SARS-CoV-2 to copy itself once it gets inside a human cell.

Antigen tests have a reputation for being unreliable, especially in people who are asymptomatic. They are considered less sensitive than molecular tests and can more often result in false negatives. That’s mostly because of detection thresholds: viral genes and viral antigens may both be needles in the haystack of our nasal swabs, but in a molecular test, that tiny amount of genetic material gets copied over and over, whereas antigen tests look for whatever bit of protein is physically in a sample. At the end of 2020, I had a significant exposure to someone with COVID-19 and experienced only mild symptoms. I tested negative with an antigen test but positive with a molecular one. Detection thresholds are most likely why.

Here’s a look at five at-home, OTC COVID-19 tests that were available to US consumers at the end of April.

Abbott Laboratories

Of Abbott Laboratories’ many COVID-19 tests, the BinaxNOW Antigen Self Test is available OTC, online and in stores. This is the test that—at least right now—the general consumer is most likely to find. Indeed, I took a quick trip around some of the major pharmacies and retailers in Dallas in mid-May, and they were available.

Abbott’s OTC test is serial. The box includes two tests—you take one, and if it’s negative, you take another within the next 36–72 h. Abbott declined requests for interviews for this story, but its test technology is fairly common. It involves a lateral flow immunoassay, in which synthetic antibodies that recognize the virus’s nucleocapsid protein are immobilized on a surface. When a person’s sample flows over the surface, those antibodies capture any viral nucleocapsid protein present. A chemical reaction either at the point of capture or further down the strip leads to a color change that, for example, creates the line or lines that indicate a positive or negative result.

The BinaxNOW Self Test wasn’t difficult generally, but there were a few tough spots. At one point, I had to place six drops from a small vial onto a test card. The vial was a little difficult to manipulate—and Radomski recognized that some of her customers with dexterity problems might struggle with this step. My card wouldn’t stay flat even after I bent the spine. The directions talk about swabbing your nose for 15 s but also say to make five rotations per nostril. Radomski said she could definitely see people swabbing too fast and timed me without my knowing it to make sure I did it right.

“This one had the most complicated directions,” she said.

Cue Health

One of the two molecular tests is made by Cue Health, which initially agreed to an interview for this story but ultimately declined.

Cue’s COVID-19 test uses an app that pairs with the testing device, which is a sleek white box that has a very Apple-product feel to it. The app walks you through the entire test and then gives you the result. The swab is smaller than the ones in other tests and has a marker to tell you how far up you should swab. It goes from your nose directly into a cartridge that fits into the testing device—unlike other tests, there’s no tube or vial of reaction fluid.

The test is based on isothermal amplification, a process by which genetic material from the virus, if present in the sample, is copied over and over at a constant temperature to reach a detection threshold. Within the cartridge, that copying step is carried out via microfluidics. But it differs from many other types of COVID-19 tests in that the readout is electrochemical. As the enzyme makes copies of the gene encoding the virus’s nucleocapsid, they stick to a sensor. When another fluid flows over that gene-coated sensor, it causes an oxidation-reduction reaction that creates a difference in current, which a circuit board translates into a positive result.

This test was simple and straightforward. After I downloaded the app and gave away a little personal information to set up an account, the instructions showed up, each needing to be completed before the next appeared. I plugged in the testing device, opened the package with the cartridge and swab, inserted the test cartridge, and waited till it warmed up. At each step, I hit a button on the app that allowed me to move to the next step. After swabbing my nose, I inserted the swab directly into the cartridge and waited for the app to give me my result.

Radomski and I both liked this test. The box contained multiple tests but only the one device. It did take a while for it to warm up, so I wondered how quickly testing would go if a school or a business had only one machine.

Ellume

Ellume’s antigen test is a lateral flow sandwich immunoassay that detects the viral nucleocapsid protein. As CEO Sean Parsons told me, the company’s test uses fluorescence as a readout, which is also used in many lab-based COVID-19 tests. Fluorescence is more sensitive than colorimetric changes or other readouts, he says.

Any nucleocapsid protein in a sample attaches to an antibody that is tethered to the surface of the test. A second antibody with fluorescent particles binds to both the nucleocapsid and the first antibody and concentrates in that part of the test. The particles are excited by ultraviolet light, and the emissions from the fluorescent dots are measured at near-infrared wavelengths.

Ellume’s testing device is a small stick, with a power button and a well. You perform the test after setting up the app and placing the testing device near your phone.

Rather than being a long stick with cottony material at the end, the Ellume swab is short and has a bumper; you insert until you feel the bumper. This was a marked difference from the other tests I tried that day—the Ellume swab went deeper, to what Parsons calls the midterminal part of the nose. It almost felt like a hospital swab. But that depth is important, Parsons says.

“Some of the other rapid tests are doing just the nostril,” he says. “We’re very worried about the performance of that. There’s pretty good data that nasal swabs are not as good as midterminal swabs. We think that’s the right spot.”

Radomski calls Ellume’s nasal swab ingenious. In her experience, it’s really hard for people to measure the ½ to ¾ inches (13–19 mm) up the nose that most companies recommend inserting the nasal swab.

There were two “huh” moments in this test. After you take the nasal swab, you have to screw it into a vial that contains the testing buffer. You then have to squeeze drops of the buffer into the well on the testing device. But an air bubble developed in the dropper tip, and when I squeezed to get it out, I overdid it, and too much liquid came out. I wasn’t sure if that would affect the test. Also, the test cannot be taken within 30 ft (9.1 m) of another Ellume test because of the connection with the smartphone app. So if more than one person in your household is taking it at the same time, you might have to go into another room for it to work properly. That detail was clear in the written instructions but not in the video, and Radomski and I wondered if people would notice it.

Lucira Health

Like a lot of diagnostics companies, Lucira Health scientists were working on an at-home flu test when the pandemic struck, so cofounder Debkishore Mitra, a bioengineer, told me it was natural to pivot their technology to rooting out SARS-CoV-2. The test, coupled with an app, has been used to check people’s COVID-19 status before they enter professional basketball games in the San Francisco Bay Area. The test uses isothermal amplification and detects SARS-CoV-2 by identifiying two nonoverlapping regions of the virus’s nucleocapsid gene.

Each time an enzyme makes a copy of that gene, a hydronium ion is released. As copies accumulate, the subsequent increase in hydronium ions drops the pH of the reaction liquid, changing its color. A microprocessor in the testing device translates that color change into a green light-emitting diode, which signals a positive result.

Radomski and I agreed that this was probably the easiest test to take and felt that it was the one that might be best adapted to resource-poor regions, because it is battery operated, and it seems as if the testing device can be used again on other samples. I appreciated that the kit included batteries. The directions asked me to tilt my head back, which Radomski said was a good way for her to see that I was swabbing far enough up my nose, as well as circling the swab around my nasal cavity—something many tests require for a good sample.

“An excellent view,” she told me. “I can really tell you are going the whole way around.”

Quidel

Quidel’s antigen test, QuickVue, works like Abbott’s BinaxNOW, using a lateral flow immunoassay to detect the SARS-CoV-2 nucleocapsid. If that viral protein is present in the sample, a piece of it—the antigen—binds to an antibody that is coupled to a red dye. That protein-antibody complex continues to travel up the strip and binds to another, presumably immobilized antibody that concentrates the red dye so it shows up as a result. Further up the strip is a control line that shows that the strip absorbed the sample properly.

Like BinaxNOW, QuickVue is a serial test. It’s being used in community projects like the one Brigham is involved in—she took periodic QuickVue tests over the course of a week to help gather data for the study embedded in the project. She never tested positive. Quidel did not respond to requests for an interview.

When I unfolded the directions, which are in English and Spanish, I immediately said, “Step 11?” The test has 13 steps. Radomski laughed. “I put, ‘Complex’ in my notes,” she said.

The video instructions, accessed from a QR code on the back of the box, turned out to be easier to follow.

So I used the video instead of the printed instructions. With the swab up my nose, I had to fight the urge to sneeze. I stirred the nasal swab in a tube of liquid and set a timer for 1 min, as directed. I then pulled out the swab, rubbed the sides on the edge of the tube to squeeze out any residual liquid, and put in the detector strip. The strips look a bit like the ones you might see in a nondigital ovulation kit or pregnancy test. Ten minutes later, I pulled the strip out and compared it with the images in the instructions.

After a couple of hours of running from one corner of my kitchen to another, ferrying Radomski around on the laptop, the tests were done. And, as I’d hoped, the tests all came out negative. I’ve been pretty religious about wearing a mask when I’m out of the house and hadn’t had any known exposures leading up to that morning. The next day, I got the lab test results—also negative.

As the US Centers for Disease Control and Prevention relaxes mask recommendations for vaccinated people, as summer camps fill up again, as companies announce more employees are returning to offices and schools go back to in-person learning, it’s plain to see why at-home tests could be a welcome alternative to pharmacy drive-throughs and doctor’s offices. But can we trust the results? Can we trust that people who use the serial tests from Abbott and Quidel will actually wait until they get two negative tests to resume “normal” life? Parthasarathy says that one thing she worries about is how our disjointed testing will affect the average American’s trust in both our COVID-19 response and health care in general.

Radomski predicts that between 50 and 75% of her customers will be able to take these tests without much trouble. And she believes that if they are paying for a test, they will sequester themselves in the event of a positive result. But being able to successfully complete the tests is a function of how well they understand the directions, not to mention the point of the test, and why testing might be important, she says. And none of the tests address consumers’ low frustration threshold. At the first sign of trouble or misunderstanding or inconvenience, she says, they’ll blow it off.

“Like, they’ll open it and see that it has 11 steps,” she says, referring to our reaction when we opened the Quidel instruction booklet and found 13 steps. “And just go ‘Gah’ and do it the way they think it needs to be done.”

Or they won’t take the test at all.

COVID-19 has disproportionately affected Black and Latino people, and especially people with low incomes. Access to testing has been a global issue since the pandemic began, and as with vaccines, the accesibility gap between developed and developing nations continues to thwart efforts to contain SARS-CoV-2. In the US, access to testing has been a challenge for people nationwide who lack transportation, time off work, or as Parthasarathy notes, trust in our country’s COVID-19 response. In the earliest days of the pandemic, I would check my county website and see that our lower-income zip codes were always the ones with the highest infection numbers.

Where there is a lack of trust, says Eveangel Savage, a community health organizer in Pitt County, North Carolina, there is a lack of testing. In her mostly rural community, not everyone has access to transportation, and a historic mistrust of medicine means people might be less likely to take a COVID-19 test that feels invasive or requires a trip to a doctor or a clinic.

Pitt County is the site of a community-based testing project using Quidel’s at-home kit and organized by the county public health department, Duke University, the CDC, and the RADx program.

Savage says that as part of the project, anyone who feels they might have been exposed to someone with COVID-19 can order an at-home test or pick one up at locations that include churches, community centers, multicultural offices, and the American Legion. She has even dropped them off on people’s doorsteps.

“Meeting people where they are is a big leader in this process,” whether physically or emotionally, Savage says. And however complicated it may make public health monitoring, no one needs to report their results, which she hopes alleviates some of the residents’ fear that personal information will be misused.

Savage believes the program, just a few weeks old but with 15,000 tests already sent out, is working. The project has two main goals, she says. One is to reduce health disparities, to get people tested early, and to help people monitor their COVID-19 exposure. The other, she says, is fairly straightforward.

“Stop the spread.”