Where’s My At-Home Molecular COVID Test?

Free rapid antigen testing kits will soon begin arriving in mailboxes across the United States—and for many Americans, the at-home COVID-19 diagnostics could not come soon enough.

Demand for the self-tests has surged amidst the wave of infections and hospitalization fueled by the highly transmissible Omicron variant. And few people want to wait in long lines for PCR testing, which remains the most accurate means of detecting positive cases but requires processing in a centralized laboratory that can be slow to return results.

Mind you, there are more than those two testing options—although, judging by news reports and health information websites, you’d be hard-pressed to know that.

A third technology known as isothermal amplification is available that offers PCR-quality molecular results with the speed and convenience of at-home antigen testing. Three companies—Cue Health, Detect, and Lucira—now sell these types of COVID-19 testing kits direct to consumers

As Nathan Tanner, a senior scientist at New England Biolabs (NEB), explains: “You can take the test at home, wait 30 minutes, and have a level of confidence in your results that you would get from a PCR test.”

The only real downside, in his view, is the platform’s cost.

Although life-science reagents suppliers like NEB sell research-grade isothermal amplification kits for less than US $2 per test, the sticker price for consumer assays range from $50 to $75 a pop (with an additional one-time hardware cost of between $25 and $250 for some commercial products).

That per-test cost compares favorably with other molecular approaches such as PCR, which often sells for $100 or more, but is well above the $12 or so associated with most rapid-antigen assays, which pick up specific proteins (termed antigens) on the surface of viral particles. Up to eight of those cheaper—but less accurate—antigen tests are now insurance-reimbursable in the United States each month as well.

“People will pay a premium for molecular performance,” Tanner says.

The question is: How much are they willing to fork out?

Isothermal techniques work similarly to PCR, in which viral genetic material is copied over and over again until a detection threshold is reached. But isothermal approaches don’t require any preparation steps to purify samples.

What’s more, whereas PCR requires expensive equipment to heat and cool the sample dozens of times to reach a detection threshold, isothermal methods take advantage of special enzymes that can operate at just one temperature, usually around 65 °C.

A couple of double-A batteries—or even hand-warmer packets and an insulated thermos—are all it takes then to make the reactions run.

Results can then be read by eye using color-changing reagents or lateral-flow assays common to home-pregnancy tests, although companies that sell these types of COVID-19 testing kits generally incorporate some sort of printed circuit board that helps convert the signal into, say, a glowing light-emitting diode for ease of operability.

And it typically takes only about 20 to 30 minutes—or at most, an hour.

“It looks very easy, unintimidating, almost unimpressive,” says Erik Engelson, president and CEO of Lucira Health, maker of the Check It COVID-19 test (which uses a form of the technology known as loop-mediated isothermal amplification, or LAMP for short). “And the steps to using it are very simple: It’s just swab, stir, and click.”

“But,” Engelson adds, “what’s going on inside is incredibly sophisticated.”

In the view of John Schellenberg, a molecular microbiologist at the University of Manitoba, in Canada, isothermal testing provides the best of both worlds, offering PCR sensitivity with rapid-antigen usability, which could be especially useful in the face of Omicron.

The now-dominant variant tends to make people contagious much sooner after infection—and at lower viral loads—compared to previous forms of SARS-CoV-2, the coronavirus that causes COVID-19. That means reporting delays from PCR results, or the inability of antigen testing to pick up trace amounts of virus, could fuel unwanted disease spread.

“And so, a more sensitive and rapid test like LAMP would be much better, because it would be able to quickly capture small amounts of virus,” Schellenberg says.

The clientele for isothermal testing during the pandemic to date has mostly been businesses, sports leagues, and hospitals looking for PCR alternatives with a quicker turnaround time.

For example, the National Basketball Association and Major League Baseball both use Cue Health’s tests to regularly screen players, team staff members, and league officials. The U.S. government, Google, and the Mayo Clinic are all Cue patrons as well, as are many schools, prisons, and local health departments—which helps explain how annual revenue for the diagnostics company exceeded $600 million last year.

Cue’s molecular COVID-19 test and appCue Health

“It’s used in many, many different scenarios by really discerning customers who care about performance,” says Ayub Khattak, cofounder, president, and CEO of Cue Health, which is also developing at-home molecular tests for influenza and other respiratory viruses.

Where it is not used as much is as a consumer substitute for rapid-antigen testing among people heading to family gatherings, attending church services, boarding flights, or going about other social activities that carry a risk of disease transmission. In those settings, rapid-antigen testing can provide a false sense of security, while PCR diagnostics are often inaccessible.

Isothermal testing offers “a no-compromise solution,” Khattak says.

“It would be nice if more people had access to it,” he adds.

Part of the problem is scalability. The technology is relatively new—developed for research purposes only around 20 years ago—and according to Engelson, “demand far exceeds manufacturing capacity.”

Lucira is aiming to produce 1 million tests per month by the middle of 2022. Across the United States, people currently run more than 3 million tests each day.

But price remains an obstacle, too. At-home molecular diagnostics will likely always cost more than antigen testing, Engelson says. “But as volumes come up, to the extent that we can make this more affordable, we absolutely will.”

At a certain price point, he and others predict that most people will gravitate to isothermal platforms.

“ ‘At-home test’ seems to be synonymous right now with rapid-antigen test,” notes Robert Meagher, a chemical engineer at Sandia National Laboratories, who has worked on LAMP-based diagnostics for mosquito-borne pathogens such as West Nile virus and Zika.

But should another variant emerge or a new pandemic strike, he expects that affordable isothermal test kits will become widespread and mainstream.

Could governments even one day be sending free isothermal test kits to households around the world? “I see that as quite possible,” Meagher says.

As Engelson bullishly proclaims: “Home testing of molecular quality is the future.”