If the story of the United States’ initial response to the novel coronavirus was one of federal health agencies utterly failing to provide enough testing, the story of the next phase is of the same organizations trying like hell to catch up. Just over a month ago, the Trump administration shifted away from its previous heel-dragging and started pushing testing more aggressively, allowing more labs to screen people for the disease. Instead of sending every sample from around the country to CDC headquarters in Atlanta, as the FDA required in February, health care workers could send samples to many other labs to have the analysis done.
But while the capacity is headed in the right direction, it’s just not enough yet. Some people are still waiting up to two weeks for test results–more than enough time to go from reasonably healthy to dying of Covid-19. Most samples are analyzed at labs run by large companies like Quest Diagnostics and LabCorp that process big quantities of diagnostic tests. But sending out the samples, waiting for them to be processed, and getting the result takes hours or even days. Sometimes samples aren’t sent individually and have to wait to be sent with a batch. It’s essentially a smaller version of the same problem that we had before: Instead of a single bottleneck at the CDC, there are many smaller bottlenecks around the country.
A new trend promises to open up these bottlenecks. A wide range of companies are developing tests that can be deployed to hospitals, doctor’s offices, airports and–maybe–even people’s homes. These machines, generally the size of a countertop kitchen appliance, can be used to test patients right at the point of care, yielding results within an hour. The FDA, in full catch-up mode, has recently handed out emergency approvals for four of these decentralized testing platforms, which are starting to expand and diversify testing capabilities. These emergency approvals let companies provide testing based on preliminary data on the devices, before the conclusion of a lengthy FDA review, for as long as the health emergency continues.
On March 20, molecular diagnostics company Cepheid received the first FDA approval for a fast, point-of-care Covid-19 test. The test comes as a $35 flip-top plastic cartridge, about the size of a roll of half dollars, that plugs into the company’s existing GeneXpert devices. While most other systems require a health care worker to unceremoniously insert a cotton swab deep into the sensitive parts of the patient’s nose or throat, Cepheid’s system can also work with a sample retrieved through a more gentle nasal wash (think: neti pot), said Cepheid chief medical officer David Persing, though it remains to be seen whether people will actually prefer that. The health care worker then puts the sample in liquid in a specimen transfer tube and uses a pipette to move it into a small tube in the cartridge that holds the testing reagents, or ingredients. Then they pop the cartridge into the GeneXpert, a sleek gray box that looks like an external hard drive array. From there the machine takes over, using microfluidics–tiny plumbing–to guide the chemical reactions along; 45 minutes later, the device reports its result to a connected computer.
The Covid-19 diagnostic relies on real-time PCR, like most others in use now, just faster. A PCR, or polymerase chain reaction, test makes a diagnosis by looking for the unique genetic sequence of the SARS-CoV-2 virus that causes Covid-19. Persing said the main use case for the Cepheid device will be at crowded hospitals that need to quickly test patients and health care workers to minimize risk to other people. There are 5,000 GeneXpert devices already in use in the US and 23,000 around the world, which were originally designed to diagnose diseases like tuberculosis and flu. The company started shipping tests this week and will produce millions more over the next few months.
On March 27, the health care giant Abbott Laboratories got the FDA’s blessing for a coronavirus test that set a new standard for speed: It shows positive results in five minutes and negatives in 13. The test runs on the ID NOW platform, which is the most common molecular point-of-care instrument in the country, according to Norman Moore, head of scientific affairs at Abbott. There are already 18,000 ID NOW devices in ERs, doctors’ offices, and urgent-care clinics around the country, helping to quickly diagnose respiratory diseases. The platform is a wedge-shaped device that looks like a futuristic alarm clock and weighs about seven pounds, portable enough that it could be used far beyond hospitals. “The instrument allows immediate access to where patient testing is needed most, taking the fight to the front lines in a variety of health care settings,” Moore said, “like drive-through testing facilities or airports. Its speed and portability can help front-line workers battle this pandemic head on.”
To perform the Covid-19 test, a clinician swabs the patient’s nose, throat, or airway deep inside the nose, then dunks the swab in the ID NOW test cartridge, where a chemical solution breaks open the virus and releases its RNA. The system then runs through the PCR process to identify the coronavirus’ unique sequence. It saves time by amplifying nucleic acids at one temperature, rather than the lengthier process of “thermocycling” used in conventional routines, said Moore. Abbott began shipping 50,000 tests per day starting on April 1 and intends to supply more than 1 million per month.
One of the more creative efforts comes from Mammoth Biosciences, a startup that aims to eventually allow people to test themselves for Covid-19 at home, as with over-the-counter pregnancy and strep tests. Mammoth’s approach relies on Crispr technology, which is usually seen as a method for snipping and editing genes. “We think about Crispr as molecular biology’s search engine. It’s not just scissors,” said Mammoth CEO Trevor Martin. The key part of the test involves adding two reagents to a patient sample: a cutting protein and a guide RNA that helps it find a distinctive piece of the coronavirus genome. Then the person running the test dunks an indicator strip into the sample. If the cutting protein finds and snips the coronavirus RNA, it then activates color-changing molecules, and two lines appear on the strip, indicating a positive result. The process takes half an hour and is about as accurate as PCR, according to Martin.
Mammoth’s test is very much a new way to do diagnosis, being worked out on the fly, with attendant advantages and drawbacks. On the upside, the Crispr chemistry is much simpler than PCR; the company’s white paper demonstrated that its method could detect the novel coronavirus on a kit jerry-rigged from off-the-shelf hardware that you might find in a public high school chem lab: a pipette, heaters for controlling reaction temperature, and a disposable paper test strip that costs less than $3. This quick test doesn’t require a fancy, proprietary diagnostic tabletop machine–any lab could get the test running quickly and cheaply. But it also requires more skill and hands-on time than Cepheid’s or Abbott’s platforms.
