Value of Nearly Instant COVID-19 Tests Is Measuring Contagion Well

One way to avoid massive shutdowns to stem COVID-19 infections is to use quick turnaround testing, according to a new study. The authors suggest that those who test positive would isolate, allowing others who testing negative to go on with their lives. Find out why researchers argue that rapid results are much more important than test accuracy in that scenario.

BOULDER, CO – Getting results almost immediately – and having those who test positive for COVID-19 isolate -- outweighs the benefits of high accuracy in novel coronavirus assays.

That’s according to an article in ScienceAdvances. University of Colorado at Boulder-led researchers suggest that testing half the population weekly with inexpensive, rapid-turnaround COVID-19 tests would eliminate the virus within weeks. And, add the researchers and their colleagues from Harvard University, it doesn’t matter that much if test sensitivity falls short of the gold standard.

The strategy would enable to the use of "personalized stay-at-home orders" that wouldn’t require shutting down restaurants, bars, retail stores and schools, the authors posit.

"Our big picture finding is that, when it comes to public health, it's better to have a less sensitive test with results today than a more sensitive one with results tomorrow," explained lead author Daniel Larremore, PhD, an assistant professor of computer science at CU Boulder. "Rather than telling everyone to stay home so you can be sure that one person who is sick doesn't spread it, we could give only the contagious people stay-at-home orders so everyone else can go about their lives."

The authors point out that, because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, robust population screening is the best way to assure the re-opening of societies while controlling the virus. They note that, after infection, COVID-19 patients usually have a period of incubation during which viral titers often are too low to detect. After that, exponential viral growth occurs, leading to a peak viral load and infectiousness before concluding with declining viral levels and clearance.

“Given the pattern of viral load kinetics, we model the effectiveness of repeated population screening considering test sensitivities, frequency, and sample-to-answer reporting time,” according to the researchers. “These results demonstrate that effective screening depends largely on frequency of testing and the speed of reporting and is only marginally improved by high test sensitivity. We therefore conclude that screening should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.”

Those conclusions were based on mathematical modeling to forecast the impact of screening with different kinds of tests on three hypothetical scenarios: in 10,000 individuals. The assumptions included a university-type setting of 20,000 people in a city of 8.4 million.

For example, in one scenario in a large city, widespread twice-weekly testing with a rapid but less sensitive test reduced the degree of infectiousness, or R0 ("R naught"), of the virus by 80%, according to the results, which also note that twice-weekly testing with a more sensitive PCR (polymerase chain reaction) test, which takes up to 48 hours to return results, reduced infectiousness by only 58%.

Researchers emphasize that, when the amount of testing was the same, the rapid test always reduced infectiousness better than the slower, more sensitive PCR test.

"This paper is one of the first to show we should worry less about test sensitivity and, when it comes to public health, prioritize frequency and turnaround," said senior co-author Roy Parker, director of the BioFrontiers Institute and a Howard Hughes Medical Institute investigator.

Background information in the study explains that antigen tests require a relatively high viral load - about 1,000 times as much virus compared to the PCR test -- to detect an infection. The RT-lamp (reverse transcription loop-mediated isothermal amplification), can detect the virus at around 100 times as much virus compared to the PCR, the authors write, while the PCR test requires as little as 5,000 to 10,000 viral RNA copies per milliliter of sample. That means PCR can catch the virus very early or very late.

One concern has been that rapid tests might miss cases early in infection, but Parker points out that an infected patient can go from 5,000 particles to 1 million viral RNA copies in 18 to 24 hours, adding, "There is a very short window, early in infection, in which the PCR will detect the virus but something like an antigen or LAMP test won't.” During that time, he adds, patients often aren’t contagious.

Senior co-author Michael Mina, MD, PhD, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, put it another way. "These rapid tests are contagiousness tests," he said. "They are extremely effective in detecting COVID-19 when people are contagious."

He added that the rapid tests can cost as little as $1 each and return results in 15 minutes, while some PCR tests can take several days. If simple, inexpensive DIY tests were sent to every home and Americans tested themselves weekly, immediately self-isolating if positive, Mina says, "Within a few weeks we could see this outbreak going from huge numbers of cases to very manageable levels.”

"It's time to shift the mentality around testing from thinking of a COVID test as something you get when you think you are sick to thinking of it as a vital tool to break transmission chains and keep the economy open," Larremore added.

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