LONDON – A huge row has broken out in the U.K. about the accuracy and utility of COVID-19 lateral flow tests (LFT) in screening asymptomatic people, as a pilot field study indicated sensitivity is less than 40%, and a nationwide roll out already is in train.

At present 116 areas of the country are due to implement community testing from next month, health care workers are due to be handed personal LFT supplies to test themselves twice a week, and the government is about to mandate use of the tests in schools after Christmas.

Field pilots were set up in November to assess the use of 20 million LFTs the government purchased from Innova Medical Group Inc., of Monrovia, Calif. All universities in the country tested students before they returned home at the end of term, and in a mass pilot in Liverpool 25% of the city’s residents took up the offer of a lateral flow test between Nov. 6 and Dec. 9.

The headline finding from the Liverpool pilot, reported on Dec. 23, is that sensitivity of the Innova test was 40%. That is some way short of the preceding validation studies conducted by Public Health England’s Porton Down Laboratory and Oxford University. When performed by trained staff the test was 76.8% accurate; in the hands of self-trained members of the public it was 73% accurate.

Meanwhile, between Dec. 2 and 9, of 7,189 students tested with the Innova diagnostic at Birmingham University, two came back positive. But when 10% of the negative tests were assessed by polymerase chain reaction (PCR), six false negatives were found, implying 60 positive cases were missed and suggesting only 3.2% of those infected with SARS-CoV-2 were correctly given a positive result.

Across all universities in Scotland 43,925 Innova tests were administered, of which 79 were positive. But of 31 people who subsequently had a PCR test, only 13 were confirmed positive, putting 58% of the Innova positive results in doubt.

LFTs are “not ready, they’re not fit for purpose,” said Jon Deeks, professor of biostatistics at Birmingham University, who carried out the analysis of the university’s testing program. “Not checking whether a test is fit for the purpose to which it is about to be put, is madness and dangerous,” Deeks said.

That view was echoed by Alexander Edwards, associate professor in biomedical technology at Reading University, who said community testing comes with complications. People operating the tests are less experienced and the test results are assessed by eye. “Many past studies using the same lateral flow technology read by eye have shown that visually recording test results can show variability [. …] For many mass testing services rolling out, there is no way the service can be properly checked for accuracy,” Edwards said.

The Innova test rose to the top of the pile from more than 130 tests considered in an initial review, in the search for a reliable LFT that was carried out by Public Health England and Oxford University. Of these 130, nine performed to the required criteria.

The LFTs under consideration identify the presence of SARS-CoV-2 proteins – in the case of Innova’s LFT detecting nucleocapsid proteins – using conjugated antibodies. That is expected to make them more accurate than first generation LFTs, which test for human antibodies (IgG/IgM), and so are reliant on the host immune response.

LFTs offer advantages over PCR testing, with no need for laboratory testing, faster turnaround, lower cost and the ability to use them in community testing of people who are asymptomatic.

In addition, LFTs testing for viral proteins are better indicators of infectiousness than yes/no PCR tests, according to Tim Peto, professor of medicine at Oxford University, who was part of the evaluation team. “PCR shows only positive or negative,” Peto said. “People who have had COVID-19 can have fragments of RNA circulating for months.”

It is possible to assess infectiousness from PCR, by looking at the number of cycle times it takes to produce enough RNA for testing, but that assessment is not done routinely. However, the evaluation team did use this metric to assess how good the Innova test is at picking out those people who are most infectious.

Iain Buchan, dean of the institute of population health at Liverpool University, who is leading the evaluation of the pilot in the city, said that although the Innova diagnostic detected only 40% of PCR positive cases, it potentially picked up 66% of people with higher viral loads, who are likely to be more infectious. “It picks up two thirds of infectious people, which is highly valuable,” Buchan said.

“The sensitivity was less than expected at 40%, but the time and scale gained by having a low-cost test that returns results within an hour without a laboratory is a valuable new tool for tracking COVID-19,” he added.

People are invited to take a weekly test and there is evidence that once they get used to the test procedure, accuracy increases. Repeat negative tests also increase confidence that negative really is negative.

Over the course of the Liverpool pilot to date, 1,300 cases of COVID-19 were detected in people with no symptoms. Currently a third of all new infections in the city are diagnosed with LFTs, in what has now become a routine testing service.

“We’ve reported what happened in the real world, with rapid roll out. This can only get better,” Buchan said.

On Dec. 3 Liverpool was moved down from Tier 3, at the time the highest level of COVID-19 restrictions, to Tier 2. However, Buchan said it is too soon to say if lateral flow testing helped reduce infections.

“It’s very difficult to draw a clear conclusion about the impact on infection rates, but we can say 1,300 people would otherwise have been walking around spreading the virus,” he said.

With the number of confirmed infections in the U.K. rising to 40,000 per day, the report on the Liverpool field study was published just before Christmas to push back against negative reporting about the accuracy of LFTs.

Louise Kenny, pro-vice chancellor of the faculty of health and life sciences at Liverpool University, said what she called “negative discourse” about the tests is “unhelpful, unethical and unprofessional, given we are in the middle of a public health crisis.”

External experts took a different view. Angela Raffle, consultant in public health at Bristol University said, “In brief, community testing in Liverpool was a costly undertaking and of uncertain value [. …] The take home message is that open access LFT for symptomless people is very unlikely to provide a cost-effective additional element in managing the COVID-19 pandemic.”

Paul Hunter, professor in medicine at the University of East Anglia agreed, saying, “I doubt that such a scheme as that piloted in Liverpool will have more than a marginal impact on the spread of COVID-19 in the U.K.”

The Innova test is CE marked, but the manufacturer’s instructions for use say it should only be used by trained staff. Following the evaluation by Public Health England and Oxford University, the Department of Health referred the product to the U.K. regulator MHRA for approval as a self-test device.

On Dec. 23, MHRA issued an exceptional use authorization for the Innova LFT to be used by members of the public. That opens the way to the nationwide program of community testing, due to be implemented by local authorities from January onwards.