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Infectious disease


Can the UK’s ambitious Operation Moonshot screening program for COVID-19 achieve liftoff?

Researchers question accuracy of rapid antigen tests and criticize government’s lack of transparency in multibillion-pound program

by Mark Peplow, special to C&EN
December 16, 2020 | A version of this story appeared in Volume 98, Issue 48


A photo of a man holding parts of an antigen test at a press conference.
Credit: Associated Press
British Army brigadier Joe Fossey, who led the mass COVID-19 testing pilot program in Liverpool, England, holds up components of Innova Medical Group’s antigen test at a press conference.

Matt Hancock’s optimism was running at full throttle as he addressed lawmakers in the UK’s House of Commons Sept. 10. Hancock, the government’s secretary of state for health and social care, waxed lyrical about a new wave of “simple, quick, and scalable” COVID-19 diagnostic tests that could be rolled out for routine screening in workplaces, schools, theaters, and sports venues as part of an ambitious plan to control the pandemic. “So-called Operation Moonshot, to deploy mass testing, will allow people to lead more normal lives and reduce the need for social distancing,” he promised.

Some epidemiologists have been advocating for this kind of routine COVID-19 screening since the early days of the pandemic. Conventional diagnostic testing typically targets those with disease symptoms and their close contacts, potentially missing the huge numbers of people who are presymptomatic or asymptomatic yet still infectious. In contrast, mass screening ensures that everyone in a particular location is tested regularly, whether or not they have symptoms, so that infected individuals can quarantine. This strategy has shown promise in keeping open some universities and workplaces, and the UK’s Operation Moonshot aims to extend this idea nationwide, potentially making it one of the largest such screening efforts in the world.

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But the government’s moonshot is having a troubled launch.

There is controversy around some of the tests used in the program, including the Innova SARS-CoV-2 Antigen Rapid Qualitative Test, which detects SARS-CoV-2 antigen proteins from a nose or throat swab. The lateral-flow device takes about 20 min to signal a positive result as a colored band on a cellulose strip, similar to the readout from a home pregnancy test. The government’s evaluation of the test found that, in some community testing centers, it missed almost half the positive cases identified by reverse transcriptase polymerase chain reaction (RT-PCR), the gold-standard diagnostic for COVID-19.

None of these tests are tests of infectiousness, and that’s one of the myths that is being propagated.
Allyson M. Pollock, public health researcher, Newcastle University

At a press conference Nov. 16, public health researchers expressed concerns about the spotty results, the vast sums of public money being poured into the program, and the UK government’s lack of transparency about how it selected the screening tests. They also pointed out that the government had not consulted the country’s advisory body for health screening before the program’s launch. “The Moonshot program really should be paused until the cost effectiveness and the value for money” of the various efforts underway are well established, Allyson M. Pollock, a public health researcher at Newcastle University, said at the press conference.

Despite these concerns, the government has spent billions of pounds on procuring tests for Operation Moonshot, and estimates provided to the government suggest the program may eventually cost more than £100 billion ($133 billion)—about three-quarters of the government’s entire health budget in normal times.

Countdown to liftoff

The government laid the groundwork for Operation Moonshot in August, when it tasked researchers at Public Health England—an executive agency of Hancock’s department—and the University of Oxford with evaluating a range of antigen tests. According to documents subsequently leaked to the British Medical Journal, the products the researchers selected could help screen about 6 million to 10 million people each day by early 2021. People who tested negative would receive an app-based immunity passport, allowing them to socialize more freely.

But researchers still have many questions about the selection process because so few results have been published. “That lack of transparency has been a criticism from the beginning,” says Joe Fitchett, medical director at Mologic, a diagnostics manufacturer whose antigen test is being evaluated by the government and Oxford researchers. Indeed, the Good Law Project, a nonprofit, is suing the government for not disclosing how it awarded testing contracts.

A photo of people waiting in a line.
Credit: Associated Press
People wait outside a walk-in testing center in Liverpool, England.

On Nov. 6, the UK’s first citywide screening trial began in Liverpool, England, which had a relatively high infection rate of 300 cases per 100,000 people. The Liverpool Mass Asymptomatic Serial Testing (MAST) trial aimed to reach up to half a million people—the city’s entire population—and relied mainly on the Innova test. Yet when the trial began, the government had not published any data about the effectiveness of the test or any protocol for the trial.

During the 3-week trial, thousands of military personnel administered the test at dozens of centers, and citizens were encouraged to take a test every 5 days, via nose and throat swabs, with results returned in less than 2 h by text or email. Anyone testing positive had their diagnosis confirmed or rejected by conventional RT-PCR.

Yet validation data on the Innova test emerged only Nov. 10, during a hastily arranged webinar hosted by the British Infection Association and the Royal College of Pathologists; the University of Oxford published its full evaluation report the next day.

It showed that the test had a specificity of 99.68%, meaning it produced very few false-positive results. However, its sensitivity, or how well it detects positive samples, was poorer: in the hands of researchers or trained nurses, the device caught 77% of all positive samples, but for self-trained individuals at community testing sites, that proportion dropped to 58%. “So there’s a difference in the overall antigen detection rate in different settings, which at the moment we think is caused by the degree of training,” Timothy E. A. Peto of the University of Oxford said during the webinar.

The performance of the Innova test also depended highly on the amount of virus present in the sample. In spiked samples containing roughly 100,000 RNA copies per milliliter, the test identified 95.5% of the positives; with only 20,000 RNA copies per milliliter, it identified none. “This test, and many similar tests, will miss cases when viral loads are lower,” says medical statistician Jonathan J. Deeks at the University of Birmingham.

Innova argues that this limit of detection is a feature, not a bug. “The objective of this test is to determine whether someone is infectious,” says Peter Santeusanio, vice president of product management at Innova Medical Group in California. The validation data show that the device returned a positive result for almost every sample with an above-average viral load, and Santeusanio argues this would identify people who pose the greatest risk of transmitting COVID-19. In contrast, those with the lowest viral loads—who are presumably less infectious—would get a negative result and avoid quarantine. If the test missed a presymptomatic individual whose viral load was on the rise, a subsequent test would catch the infection a few days later.

But Deeks and Pollock say there is little direct evidence that viral load is proportional to infectiousness in this way. “None of these tests are tests of infectiousness, and that’s one of the myths that is being propagated” by the UK government, Pollock says.

This repeated testing catches all those little embers that could start local fires but instead get extinguished quickly.
Daniel B. Larremore, infectious disease modeler, University of Colorado Boulder

However, Daniel B. Larremore, an infectious disease modeler at the University of Colorado Boulder, believes the Innova test could help control infections. He and his colleagues have modeled the effectiveness of a rapid antigen test operating at a similar limit of detection and sensitivity as the Innova test; they found that the frequency of testing and how quickly the results are reported are far more important than sensitivity to ensure a successful screening program (Sci. Adv. 2020, DOI: 10.1126/sciadv.abd5393).

Their model simulated a population of 10,000 people and predicted how well an outbreak could be controlled by isolating positive cases after screening with one of two tests: a rapid antigen test that can detect viral loads equivalent to 100,000 RNA copies per milliliter and an RT-PCR test that can typically detect around 1,000 viral RNA copies per milliliter.

Although the antigen test was less ­sensitive than RT-PCR, it delivered results almost instantly, while RT-PCR took up to 2 days to process. The model predicted that giving people the antigen test every 3 days would reduce the overall infectiousness of the population by about 80%. “This repeated testing catches all those ­little embers that could start local fires but instead get extinguished quickly,” Larremore says. In contrast, an RT-PCR test offered at the same frequency would reduce infectiousness by only about 50%.

“There’s been a big discussion among scientists about the validity of asymptomatic testing,” says Deenan Pillay, a virologist at University College London. “Personally, I support more aggressive screening, especially with younger populations, where a greater proportion of people are going to be asymptomatic.”

Onward and upward

While the scientific debate raged through November, the MAST pilot in Liverpool deployed more than 100,000 Innova tests, which identified about 1,000 positive cases. No results have been formally published, but preliminary data were buried in an appendix to the government’s new mass-screening guidelines, which were released Nov. 30. The report says Innova’s antigen test picked up just 5 of the 10 infections detected by PCR and “more than seven out of 10 cases with higher viral loads, who are likely to be the most infectious.” Nevertheless, Hancock has hailed MAST as a success and credits it with helping reduce the infection rate in the city to about 100 per 100,000; however, the region also implemented strict social-contact restrictions that would have significantly curbed infections anyway. So far, Innova has shipped 120 million–140 million tests to the UK, where they are being rolled out to 67 more towns and cities. The company is bidding for a new UK government contract, valued at £912 million.

Operation Moonshot is also introducing twice-weekly testing for roughly 1 million National Health Service staff, nursing-home workers, and other high-risk groups. But in early December, some local councils in the region asked nursing homes to hold off on using Innova tests, in part because staff had not yet been trained. Some health-care workers will be tested with a different assay, made by OptiGene, which relies on loop-mediated isothermal amplification (LAMP) technology to detect viral RNA. In one study, which has not been peer-reviewed, the test showed a sensitivity of 97% and a specificity of 99% (medRxiv 2020, DOI: 10.1101/2020.06.30.20142935). But it too has come under fire: a pilot of the assay in Greater Manchester in September and October suggested it has a much lower sensitivity, according to scientists in the region’s mass-testing expert group.

The overarching goal of Operation Moonshot is to ramp up COVID-19 screening to levels seen in countries like China and Slovakia. After a strict lockdown, China used mass screening of millions of people in several cities, including Qingdao and Wuhan, to quash any budding outbreaks. Those efforts have generally relied on RT-PCR and other technologies to increase throughput.

Slovakia, meanwhile, embarked on a population-wide screening effort on two successive weekends in November. Most of the testing relied on SD Biosensor’s Standard Q antigen test, which was the first rapid point-of-care COVID-19 test to receive World Health Organization approval.

Roughly 1% of people tested positive by nasal swab in the first weekend, which covered nearly two-thirds of the country’s population, and they were required to quarantine. In a preprint, which has not yet been peer-reviewed, researchers revealed that the screening program played a key role in reducing the prevalence of infection in the country by 82% and declared it “highly successful” (medRxiv 2020, DOI: 10.1101/2020.12.02.20240648).


Many researchers are skeptical about the UK government’s ability to pull off such an ambitious program. Beyond the limitations of the tests themselves, the pilot program in Liverpool suggests uptake could be an issue—in low-income areas of Liverpool, participation was as low as 4%. Critics argue the government should instead focus resources on improving the UK’s £22 billion COVID-19 testing and contact-tracing service for symptomatic people. In November, the National Health Service Test and Trace service reached only about 60% of close contacts of infected individuals. “Focusing on testing without a bigger focus on contact tracing and isolation is a bit of a waste of effort,” Pillay says.

Meanwhile, a series of COVID-19 vaccine trials has reported successes, and widespread vaccination is expected to begin in many countries early next year. So just as the UK’s mass-screening program takes off, might vaccines render it redundant? Larremore thinks not: “There’s a big role for increased testing in the time between now and next summer,” he says. “Just as I don’t think we’re going to take the masks off for another 6 months, I also don’t think we’re going to sidestep the need for testing in that time.”

Mark Peplow is a freelance science writer based in the UK.


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