Once obscure diagnostic devices, lateral flow tests have had a rocky path to mainstream use, but some experts now view their rise to ubiquity as a “heroic” step in the fight against Covid-19 and say they could be here to stay.
As the first wave of Covid crashed down in early 2020 and governments scrambled to secure PPE, ventilators and reagents for laboratory testing, behind the scenes some had already foreseen a role for the pregnancy test-style kits.
“We started thinking about it in late 2019 when we were at international trade shows where it was becoming a hot topic,” said David Campbell, the director of the Derby-based diagnostics company Surescreen, which has been in the lateral flow business for more than 25 years and brought one of the first antigen tests in Europe to market. “We’d done a lot of work on influenza and some work on Mers. We thought initially that it would be a niche product.”
The first Covid lateral flow tests were designed to detect antibodies. At the time governments optimistically – and wrongly – hoped that proof of prior infection could act as a “freedom pass” allowing people to return to life as normal in the knowledge that they were immune to the virus.
By April 2020 the UK government had announced the purchase of 17.5m lateral flow testing kits, describing them as a “gamechanger”. But this proved to be a misstep. “They absolutely didn’t work – they were awful,” said Prof Sir John Bell, Regius professor of medicine at Oxford University. (He noted that Surescreen’s test was not among these.) “There were a lot of people running around trying to sell tests that didn’t work trying to make a fast buck. It was pretty scandalous. That was the starting point for lateral flow tests.”
The orders were quietly cancelled, and Bell said one valuable lesson was the need for a robust validation process. The government established a group of Porton Down scientists, chaired by Bell, to validate tests for use.
By early autumn 2020 many companies had switched their focus to antigen tests, which use synthetic antibodies to detect proteins from the virus itself. The UK government had also moved on to Operation Moonshot, which aimed to deliver millions of these kits to people’s homes. “Whenever I hear the word ‘moonshot’ from No 10 my heart sinks,” Bell said. “But the reality is that lateral flow tests have delivered. It’s been one of the more heroic moments of the pandemic.”
This time the government fast-tracked a pilot of community testing of about 125,000 people in Liverpool using Innova’s lateral flow antigen test, and found that 897 people who did not know they had the virus tested positive and were stopped from spreading it further. Egter, the tests in the field missed 60% of infections in people who were self-swabbing, and even in those with high viral loads 30% of cases were missed.
The results were controversial, with a vocal group of scientists warning that reliance on LFTs to open up schools and the economy risked providing false reassurance.
“We were being attacked left, right and centre,” said Prof Iain Buchan, the chair in public health and clinical informatics at the University of Liverpool, who led the pilot. “It was almost a religious argument about whether you were for lateral flow testing or not. We even received death threats.”
Buchan and others saw things differently. “Those who were criticising it were seeing it as a clinical diagnostic tool, not a public health tool," hy het gesê. He and others argued that comparing the tests with the “gold standard” of laboratory-based PCR tests, which detect viral RNA, missed the point. Lateral flow tests aimed to spot people who would never have come forward for a PCR test in the first place and provide results at a fraction of the cost, in minutes rather than days.
According to analysis by Buchan and colleagues, hospitalisations in Liverpool during the second wave were around a third lower than they would have been without the use of lateral flow tests. He said this reduction could not have been purely the result of people who tested positive self-isolating, but that doing the tests prompts wider behaviour changes such as other household members behaving more cautiously.
Evidence also emerged that LFTs are most sensitive during the period when people have a high viral load, which has led some to argue they are a better test of when people are actually infectious. Egter, there is no established threshold for “infectiousness” and the sensitivity to low levels of antigens varies considerably between different brands of test.
“The supposed ability of LFTs to detect people while they are ‘infectious’ seems to have become accepted dogma, but we know from our latest review that although pretty much all LFTs are very reliable when used in people with the very highest viral loads, there is considerable variation in assay performance at lower levels,” said Jac Dinnes, a senior researcher at the University of Birmingham who is leading a review of the accuracy of lateral flow tests.
As case numbers fell in 2021, lateral flow tests also came under criticism for delivering false positives. This reflects a classic statistical conundrum: if you test positive, the chances that you really have Covid depends on not only the quality of the test but also the current prevalence of the virus. For instance, if an LFT delivers a false positive result for one in 1,000 tests at a time when just one in 1,000 people have Covid, the chances that someone with a positive is truly infected are only 50%. But if the prevalence is one in 10 mense, as it was in London last week, that person can be 99% sure they are infected.
The latter may be the clearest explanation for why lateral flow tests have come into their own at this particular juncture in the pandemic. Since the emergence of Omicron, case numbers in the UK have risen to such extraordinary levels that the issue of people having to isolate unnecessarily due to false positive results is negligible (and makes confirmatory PCR tests redundant). Vaccination has lessened the risk of severe disease and weakened the case for full national lockdowns. Yet we are still facing a pandemic that needs to be brought under control. Experts say the UK is in effect performing a huge public health trial on the extent to which mass testing can achieve this goal.
“The way that these tests have gone from a tool intended to help diagnose, or at least triage, people with symptoms of Covid-19 to something recommended for daily use in people without symptoms is really quite the story,” said Dinnes. “I have not seen any published evidence from primary studies, as opposed to modelling studies, that fully supports this policy.”
The jury is out on whether government advice to “flow before you go” will be recalled as another surreal episode of the pandemic, like Zoom quizzes and clapping for the NHS on our doorsteps, or whether it will become part of the fabric of daily life. Some say that as case rates come down, mass testing will be less valuable as a public health tool. Others believe that the pandemic will pave the way for LFTs for a wider range of respiratory viruses. In the future, hulle sê, parents might do a quick test on their child before sending them to school when they wake up with a slight cough, or an elderly person might test for flu and take antiviral tablets before the symptoms really kick in.
“There’s a world where these could be quite transformational … in which you could change the impact of respiratory viruses in society generally,” said Bell.