OFrom obscure diagnostic devices, lateral flow tests have had a difficult path to widespread use, but some experts now see their ubiquity as a ‘heroic’ step in the fight against Covid-19 and say they could be there to stay.
As the first wave of Covid collapsed in early 2020 and governments rushed to secure PPE, ventilators and reagents for lab tests, behind the scenes some had already planned a role for the kits. pregnancy test style.
“We started thinking about it in late 2019 when we were at international shows where it was becoming a hot topic,” said David Campbell, director of the Derby-based diagnostics company Surescreen, which has been in the sidestream business for over. one year. over 25 years and brought to market one of the first antigenic tests in Europe. “We had done a lot of work on the flu and a bit on Seas. We initially thought it would be a niche product.
The first Covid lateral flow tests were designed to detect antibodies. At the time, governments optimistically – and mistakenly – hoped that evidence of a previous infection could serve as a “freedom pass” allowing people to resume normal lives knowing they were immune to the disease. virus.
In April 2020, the UK government announced the purchase of 17.5m lateral flow test kits, describing them as a ‘game changer’. But that turned out to be a misstep. “They absolutely didn’t work – they were awful,” said Professor Sir John Bell, Regius Professor of Medicine at the University of Oxford. (He noted that Surescreen’s test was not one of those.) “There were a lot of people trying to sell tests that didn’t work by trying to make a quick buck. It was quite outrageous. This was the starting point for the lateral flow tests.
Orders were quietly canceled, and Bell said a valuable lesson was the need for a robust validation process. The government created a Porton Down group of scientists, chaired by Bell, to validate the usability tests.
By early fall 2020, many companies had focused on antigen testing, which uses synthetic antibodies to detect proteins in the virus itself. The British government had also moved on to Operation Moonshot, which aimed to deliver millions of these kits to people’s homes. “Every time I hear the word ‘moonshot’ from number 10, my heart sinks,” Bell said. “But the reality is that the lateral flow tests have given results. It was one of the most heroic moments of the pandemic. “
This time the government accelerated community test pilot of about 125,000 people in Liverpool using Innova’s lateral flow antigen test, and found that 897 people who were unaware they had the virus tested positive and were prevented from spreading it further . However, field tests failed 60% of infections in people who swab themselves, and even in those with a high viral load, 30% of cases go undetected.
The results were controversial, with a group of scientists warning that using LFTs to open schools and the economy could provide false assurances.
“We were attacked from left, right and center,” said Professor Iain Buchan, chair of public health and clinical informatics at the University of Liverpool, who led the pilot project. “It was almost a religious argument as to whether you were for the lateral flow test or not. We have even received death threats.
Buchan and others saw it differently. “Those who criticized it saw it as a clinical diagnostic tool, not a public health tool,” he said. He and others argued that comparing the tests with the “gold standard” of laboratory PCR tests, which detect viral RNA, was irrelevant. Lateral flow testing aimed to spot people who would never have shown up for a PCR test in the first place and deliver results at a fraction of the cost, in minutes rather than days.
According to Buchan and colleagues’ analysis, hospitalizations 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 be purely the result of people who have tested positive for self-isolation, but that doing the testing prompts broader behavior changes, such as other household members falling into the trap. behaving more cautiously.
Evidence has also emerged that LFTs are most sensitive during the time people have a high viral load, leading some to argue that they are a better test to determine when people are actually contagious. However, there is no established threshold for “infectivity” and sensitivity to low levels of antigens varies widely between different brands of test.
“The supposed ability of LFTs to detect people when they are ‘infectious’ seems to have become accepted dogma, but we know from our latest review that although virtually all LFTs are very reliable when used in people with the highest viral loads, there is considerable variation in test performance at lower levels, ”said Jac Dinnes, senior researcher at the University of Birmingham who is leading a review of the accuracy of flow tests lateral.
As the number of cases declined in 2021, lateral flow testing has also come under fire for providing false positives. This reflects a classic statistical conundrum: If you test positive, the chances of you actually having Covid depend not only on the quality of the test but also on the current prevalence of the virus. For example, if an LFT provides a false positive result for one in 1,000 test at a time when only one in 1,000 people has Covid, the chance of a positive person being truly infected is only 50%. But if the prevalence is one in 10 people, as was the case in London last week, that person can be 99% sure they are infected.
The latter may be the clearest explanation for why lateral flow testing has become imperative at this particular stage of the pandemic. Since the emergence of Omicron, the number of cases in the UK has reached such extraordinary levels that the problem of people needing to self-isolate unnecessarily due to false positive results is negligible (and makes confirmatory PCR tests redundant) . The vaccination reduced the risk of serious illness and weakened the case for a full national lockdown. Yet we still face a pandemic that must be brought under control. Experts say the UK is indeed carrying out a huge public health trial on the extent to which mass testing can achieve that goal.
“The way these tests have gone from being a tool meant to help diagnose, or at least sort out, people with symptoms of Covid-19 to something recommended for daily use in people without symptoms is really all the rage. ‘history,’ Dinnes said. “I have not seen any published evidence from primary studies, as opposed to modeling studies, that fully supports this policy. “
The jury is out on whether the government’s advice to ‘get around before you go’ will be remembered as yet another surreal episode of the pandemic, like the Zoom quizzes and clap for the NHS on our doorstep, or whether they will become part of the fabric of daily life . Some say that as case rates drop, mass testing will be less useful as a public health tool. Others believe the pandemic will pave the way for FTLs for a wider range of respiratory viruses. In the future, they say, parents could do a quick test on their child before sending him to school when he wakes up with a mild cough, or an elderly person could test for the flu and take pills. antivirals before symptoms really appear.
“There is a world where these could be quite transformational… where you could change the impact of respiratory viruses on society at large,” Bell said.