Last week, High Level, a city of approximately 3,000 people in northwestern Alberta, Canada, received supplies of coronavirus test kits manufactured by the U.S. health agency Cepheid and the Italian company DiaSorin from the provincial health agency. The kits enable high-profile hospitals to deliver COVID-19 test results in just 30 minutes.
Prior to last week, residents of High Level, like other remote areas in the province, had to wait days for the results of the coronavirus tests because the samples had to be transported 455 miles to the nearest laboratory in Edmonton.
Test speed is a critical factor in outbreak management. Knowing whether a patient has the coronavirus means that healthcare workers know how to proceed: what treatment needs to be done? Where should patients be brought to a hospital, especially in communities with special COVID-19 wards? and whether medical personnel who see the patient should preserve or use personal protective equipment.
"The ideal (test) is something right at the bedside or the person rolls up and in a few minutes you can tell them if they have (coronavirus)," said Byron Berenger, a medical microbiologist who works in the Alberta public health laboratory, Calgary .
But this ideal is far from the norm. The most reliable tests for coronavirus detect the presence of the RNA of the virus (its genetic material), a process that takes more time than tests that show, for example, the presence of a hormone, such as a pregnancy test.
The fastest test on the market is Abbott Laboratories' ID Now test after five minutes to get a positive result. However, he was followed by allegations of inaccuracy. Cepheid and DiaSorin, whose tests were sent to High Level, have shown promise to strike a balance between speed and accuracy, but have other problems.
Private companies and public laboratories struggling to develop faster tests face obstacles such as a high rate of false negative results, manufacturing restrictions, and inexperience. Medical workers and patients have to wait hours or even days for results, which can hinder containment strategies.
A rapid test is "better for the person, better for treatment as a patient, better for detecting outbreaks," said Berenger. But "the most important thing is to diagnose accurately, and second, to achieve a faster result that people can respond to."
Speed vs. reliability
In March, US President Donald Trump stood in front of reporters on the White House lawn and unpacked Abbott's ID Now coronavirus test kit, which, according to the company's website, delivers negative results in 13 minutes and positive results in five minutes.
President Trump points to a COVID-19 test kit from Abbott Laboratories ID Now during a Coronavirus Task Force press conference in the Rose Garden of the White House on March 30, 2020. Michael Reynolds – EPA / Bloomberg / Getty Images
This processing time makes ID Now the fastest corona virus test on the market, but its reliability is questionable. In mid-May, researchers at New York University found that the test produced false negative results almost half the time. Abbott defended his test and criticized the methodology of the NYU study. However, the Food and Drug Administration later issued a warning about “possible accuracy problems” with ID Now.
A certain amount of compromise between speed and accuracy is expected, says Mike Catton, deputy director of the Doherty Institute for Infection and Immunity at the University of Melbourne. "In general, the fastest tests bring some level of sacrifice, mostly in terms of sensitivity to detection," he said.
The most reliable test is the reverse transcriptase-polymerase chain reaction (RT-PCR), which Catton calls the "gold standard detection method" for the coronavirus. Many companies and most public laboratories use RT-PCR.
According to researchers from the Foundation for Innovative New Diagnostics, a global nonprofit health organization, the tests are 96% accurate for negative samples and 100% accurate for positive samples.
But it takes time.
Extracting virus RNA from the sample – a necessary step for RT-PCR – takes 30 minutes, says Matthew Lalli, a postdoctoral fellow at Washington University, St. Louis School of Medicine.
The extracted RNA is mixed with a reagent cocktail and heated, which takes 15 minutes. Then it goes through signal amplification: 45 one-minute PCR cycles that make billions of copies of the original sample and provide a sample large enough to detect the virus.
The high sensitivity of the test depends on the amplification process; Shortening this step would mean that the likelihood of virus detection, and therefore the accuracy of the test, may be affected.
The Alberta PCR test takes 90 minutes to begin, but the time it takes to collect the sample, transport it to the laboratory, and collect enough incremental samples to start a round of the machine in large quantities runs, results in an 18 hour in the Berengers Calgary laboratory, says the scientist.
Find a balance
The Cepheid and DiaSorin tests sent to High Level are promising in that they automate or eliminate certain steps required for the standard test, saving time. The Cepheid test takes up to 45 minutes and the DiaSorin test "just over an hour," the website says. It does without the “traditional RNA extraction steps” in RT-PCR, which shave for 30 minutes.
They are also accurate: Studies have shown that the Cepheid and DiaSorin tests are at least 95.8% and 89.3% accurate.
But two factors prevent the tests from being a silver bullet. Price and offer. According to the Foundation for Innovative New Diagnostics, one of Cepheid's PCR devices costs $ 17,500 without the price of the cartridges required to operate it. And they are rare; Manufacturers could not keep up with the global surge in demand, said Berenger. None of the companies returned Fortune's requests for comments.
Faster tests also tend to have lower throughput capacity, which means that they cannot process as many samples at the same time as the slower RT-PCR tests. Abbott's ID Now processes one sample at a time, as does the 45-minute Cepheid test, while standard RT-PCR tests contain well plates that can process 96 or 384 samples simultaneously.
Lalli is one of several researchers working on another test method, loop-mediated isothermal amplification (LAMP), which is similar to PCR but does not require the resources of a centralized laboratory.
Lalli and his colleagues are building a portable device that allows patients to run a coronavirus test in a clinic or at home and deliver results within an hour. The LAMP test is "most similar to Abbott ID Now," said Lalli, "but we are making great efforts to improve the sensitivity of the virus detection." Lalli's research is still at an early stage, a preprint of the paper noted, but the results are "promising".
According to Lalli, LAMP saves about 30 minutes compared to RT-PCR. Reverse transcription and amplification take place simultaneously. In addition, the reaction is isothermal, which means that it takes place at a constant temperature and does not alternate between heating and cooling. This process extends the standard PCR procedure by time. The ID Now test is also isothermal.
Some companies are developing tests that look for antibodies (immune response proteins) or antigens (virus proteins) instead of nucleic acids. This is demonstrated in the conventional PCR tests LAMP, ID Now and the quick test kits.
Antibody and antigen tests are usually performed as lateral flow immunoassays, says Lalli, and – like pregnancy tests – are supplied as a measuring stick. With a blood or spit sample, they give a visual indication of whether the person has coronavirus. They are easy to use and deliver results in five to 10 minutes.
But they showed “really bad sensitivity” compared to PCR, said Berenger. "We speak below 80% (exactly) … So you sometimes miss 30 to 40% of the cases."
The lateral flow method skips the crucial amplification process of PCR, which saves time at the expense of sensitivity, says Lalli. There are antibody and antigen tests with signal amplification (a method called ELISA), but they take an hour or two.
Regulations Because diagnostic tests are relatively lax in most parts of the world, which means that there are "hundreds on the market" that have not passed any regulatory requirements Approval, said Berenger, and many manufacturers have no experience of performing tests for respiratory viruses.
The FDA last week prohibited 29 antibody test manufacturers from selling their products in the United States. This was a change in timing compared to April when the FDA allowed manufacturers to commercialize their antibody tests, including those that they had not yet reviewed. Also in April, the United Kingdom paid $ 20 million to two Chinese antibody testing companies that did not work.
Antibody tests are more reliable, but they measure whether you've had the virus and recovered. Therefore, they are not helpful in identifying active carriers of the disease who could spread it to others.
"In general, the fastest tests bring some sacrifice, mostly in the sensitivity direction," said Catton. "It's a balancing act that scientists are incredibly careful about."
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