Just before the COVID-19 pandemic hit, medical technology company Lucira Health was starting to fine-tune its at-home flu test.

“We found ourselves in January 2020 wondering, wow, we have this platform, should we be looking at COVID-19?” Kelly Brezoczky, executive vice president at Lucira Health, told The Verge. Most of the technology would transfer; it was just a matter of swapping in the coronavirus for the influenza virus.

By November 2020, Lucira had the first US Food and Drug Administration (FDA) authorization for a fully at-home COVID-19 test. If the company had kept working on its flu test, Brezoczky says she’s not sure if it would have been on the market by then. “Our COVID-19 product leapfrogged our first product,” she says.

Before the pandemic, small companies like Lucira and academic research labs were working on shrinking and speeding up tests that could diagnose someone’s viral infection by detecting a virus’s genetic material in a swab from their nose or throat. They wanted to make it possible for these highly accurate tests to be done in a doctor’s office, at the patient bedside, or at home. But for the most part, those systems were in early stages of development. Most of this kind of testing, known as molecular testing, still had to be done in a lab.

Skyrocketing need for COVID-19 testing accelerated all of those nascent efforts. Suddenly, the federal government and private companies were investing millions, and the Food and Drug Administration was using emergency authorizations to get tests on the market. Experts long predicted that at-home testing could be the future, but the pandemic shortened the timeline to get there.

“Overall, it was a very big opportunity,” says Paul Yager, a professor in the department of bioengineering at the University of Washington who works on rapid test development. “It sounds cynical, but a bad public health problem that gets everyone’s attention — and certainly this got everyone’s attention — pumps money into the field.”

Early development

A year ago, just as the COVID-19 pandemic was starting to accelerate in the United States, it was hard if not impossible for most people in the US to track down a coronavirus test. The country relied on a type of test called a PCR. PCR is the gold standard approach to identifying a virus. It looks for a snippet of the virus’s genetic material in a swab collected from a patient. That’s why it’s also called a molecular test: it searches out a genetic molecule.

Molecular tests are very different from another kind of viral test called an antigen test. Antigen tests look for a protein on the surface of the virus rather than the molecular code of the virus itself. They are cheap and fast, but they can be less accurate than molecular tests like PCR.

Image: Lucira Health

PCR is typically a good approach: it’s extremely accurate and easy to develop against new viruses. However, it’s finicky, takes training to handle the samples, and requires bulky, energy-sucking, expensive equipment. It’s usually run in hospitals or centralized labs. It also takes a few hours to run. During a health emergency, a few hours is too slow. And when cases spike and labs get a flood of samples, people may have to wait days to get their results.

A faster test in those situations could make a huge difference in public health officials’ ability to track down infections and cut off the spread of disease. But until the pandemic hit, there hadn’t been significant investment or focus on creating faster, simpler molecular tests. It didn’t seem as necessary. “[Rapid testing] was more on the fringes, because our normal laboratory setup in the United States was already robust,” says Jacqueline Linnes, assistant professor of biomedical engineering at Purdue University.

Small companies and academic research labs were still interested in creating those types of systems and made significant progress on the science and technology behind them. They figured out how to make gene detection energy efficient and cut down the number of steps needed to get a result. They also worked to make them easier to use by people without specialized training. But they didn’t attract interest from big companies that could push them to market at scale, Linnes says. “It was an academic exercise.”

Yager, for example, had a small molecular test that could be applied to multiple types of diseases ready in 2017. But he couldn’t get a company to work with him to commercialize the product. “It was the commercial market that actually caused the project — which was technically successful — to fail,” he told The Verge last March.

Out of the lab

The pandemic upended that pattern. Suddenly, there was funding for and commercial interest in rapid testing. The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) initiative, which funded the development of new testing technologies for COVID-19. The pandemic was a public health emergency, so the FDA cleared tests under Emergency Use Authorizations (EUAs), which allows tests to be used after shorter examination periods than usual.

“We found out that industry has all of the resources and all of the know-how to make this stuff happen — if only they have the motivation,” Linnes says.

Because researchers and small startups had already been working on rapid tests, some were able to take the same approach as Lucira and swap out their original target for the coronavirus. Visby Medical had originally developed a rapid sexually transmitted infection test, but it quickly started work on a rapid COVID-19 test that was funded through the NIH’s program. It got authorization in February 2021.

Image: Visby Medical

The FDA authorized the first rapid molecular tests, made by the medical technology companies Cepheid and Abbott, in March 2020. Both can be used in health centers, nursing homes, or urgent care clinics close to patients. They take a specialized machine, but samples don’t have to be sent out to a lab. Many rapid tests use that approach: they have to be done by medical professionals but right at the location where patients get swabbed.

Visby’s test falls into that category. It has a single-use cartridge that can be used in environments like nursing homes and some schools. Eventually, Visby hopes its tests can be used at home, says Adam de la Zerda, founder and CEO of Visby Medical. The FDA has already cleared a handful of at-home COVID-19 tests, including Lucira’s. Last week, the agency authorized another at-home molecular test from the medical technology company Cue. Unlike Lucira, Cue’s test doesn’t require a prescription.

Yager thinks there will be more of a push for at-home testing. “They’re not all approved for home use yet, but that’s generally the direction that the FDA went — and I think it’s a trend,” he says.

The future of diagnostics

Rapid molecular tests are still only available in extremely limited quantities. Lucira is still scaling its production lines, and Cue hasn’t announced when its COVID-19 test could be on shelves. But they’ll be more and more available over the next year and could usher in a new approach to disease testing overall. “Today the model is that you schlep your way over to a hospital, or stand in a long line in a waiting room, and it takes a day. That’s not the way we want to go forward,” Yager says.

The increased interest and money in rapid molecular testing is already making a huge difference for smaller companies and academic labs. Lucira became a publicly traded company in February and is worth over $400 million. That raised a lot of eyebrows, Yager says. “The fact that there’s now a game for the investors to get into is a very exciting thing.”

Moving disease testing out of the lab would make diagnoses for diseases other than COVID-19 easier. It would also help people start treatment early. There are treatments for the flu, for example, that work well — but only if people start them within a day or two of feeling symptoms.

Normally, most people don’t go to the doctor in that window, says Lucira’s Brezoczky. That’s what Lucira’s flu test — which the company is still planning to launch — aimed to help with, she says. If people could buy an accurate test when they went out to buy cough medicine, they’d be able to know if antivirals would help. “Then, you actually have a chance to reduce both duration and severity of symptoms,” she says.

Visby also hopes to get clearance for its sexually transmitted infection test this year. Like the flu, those types of conditions are easier to treat if they’re caught early.

Rapid molecular tests are still expensive, Linnes says. Lucira’s COVID-19 test is $50. Cue hasn’t set a price for its newly authorized at-home molecular test. At this point, the price of these tests might be too high for regular cold and flu season use. But eventually, mass production and broader use could lower the price and help them become more commonplace, Linnes says.

Apart from price, a big advantage of scaling rapid molecular test manufacturing would be building a foundation for the next public health emergency. If the tests were in regular use for more ordinary viruses, it would be easier to adjust them to test for a pandemic virus, Linnes says. The US wouldn’t be as reliant on the slower in-lab PCR.

That only happens, though, if the investment and interest in these systems continue. Sliding back into the status quo of lab-based testing after the COVID-19 pandemic fades, and not taking advantage of the momentum for at-home testing, would leave everyone in the same position they were in a year ago. “We need to continue the investment,” Linnes says.

The COVID-19 pandemic showed how important it is to be able to quickly and accurately diagnose diseases, de la Zerda says. He thinks there will be more focus on rapid molecular testing so that governments are prepared for new viral threats. They could have made a big difference at the start of this pandemic. “If we had access to these tests in high volumes, we probably would be in a very different position right now,” he says. “We certainly would not be at the level of 500,000 deaths in this country.”

https://www.theverge.com/2021/3/10/22323268/covid-rapid-testing-pandemic-home-disease-pcr