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The Guardian - UK
The Guardian - UK
World
Linda Geddes Science correspondent

Covid tests: how can people be positive on lateral flow and negative on PCRs?

Anna Brading with her son
Anna Brading with her son, who repeatedly tested positive using lateral flow tests, only to go on and test negative with PCRs. Photograph: David Levene/The Guardian

Lateral flow tests (LFTs) are an increasing part of our everyday lives. But for some individuals, a persistent clash with their PCR test results is undermining their confidence in the system.

The Guardian has been contacted by hundreds of people who have repeatedly tested positive on lateral flow devices (LFDs), but whose confirmatory PCR tests have been relentlessly negative.

Amy Lewis’s son Josh, nine, has tested positive on LFTs six times in the past eight months. “The biggest implication was that we were supposed to go to Guernsey to see my family for Christmas, but we decided not to go, because [of the testing requirements]. We couldn’t put Josh through the emotional upheaval of that,” said Lewis, from Bristol. “What has been frustrating is the lack of recognition that this is an issue, or that it might be possible.”

Anna Brading of Reading received a warning from her son’s headteacher, because he had missed so much school as a result of having to self-isolate. “We have no way of telling when he actually gets Covid and I have vulnerable family members that we want to see,” she said.

Barbara Mann, 35, of Monmouth, believes her LFTs may be detecting some other virus. “There are always two lines, sometimes the second is faint, sometimes strong,” she said. “It seems to depend if I’m feeling under the weather or not.”

Scientists stressed that, because no test is 100% accurate, some contradictory results should be expected – but for those with multiple conflicting results, something else could be going on. “It is important that we get to the bottom of this to resolve the uncertainty for the people whose lives are being thrown into confusion by these seemingly erroneous results,” said Dr Kit Yates, a mathematical biologist at the University of Bath.

So, what are the possible explanations?

Statistical anomaly

With so many LFTs and PCR tests being done at the moment, some people will get a run of false positives and false negatives, even though the statistical probability of this is low. “The main reason people may get a mismatch between a LFT and PCR is likely to do with the sensitivity and specificity of the tests,” said Irene Petersen, a professor of epidemiology and health informatics at UCL. “In short, when we have a high prevalence of Covid, as we do right now, it is much more likely that a positive LFT is correct than a negative PCR test is correct.”

Nevertheless, the chances of people randomly testing positive on multiple lateral flow tests over long periods of time and without symptoms is extremely low, said Yates. “Consistent false negatives – perhaps due to poor swabbing technique – would be easier to explain away, but not false positives.”

Testing errors

In October, UKHSA suspended PCR testing at a laboratory in Wolverhampton after an investigation into reports of people receiving negative PCR results after a positive LFT. “Hopefully that isn’t happening again,” said Alexander Edwards, associate professor in biomedical technology, at the University of Reading.

Another possibility is that the swab collected for the PCR test was inadequate, or that by the time the PCR test was taken, the infection had gone away.

Test cross-reactivity

The simplest technical explanation would be some kind of interference in the assay – similar to reports of schoolchildren pouring orange juice or cola on their LFTs to fake a positive Covid test. “It’s thought that acid or acidic solutions can cause the antibodies in the test which detect Covid to clump together, which may appear to give a positive result,” Yates said. “One potential hypothesis, therefore, is that these false positive could be related to people’s diets. This is why the tests suggest you don’t take them until at least 30 minutes after eating.”

Cross-reactivity with other circulating coronaviruses could also be a possibility, Yates said. “These are all just hypotheses though. In reality we will need to undertake a more detailed study to understand why some people consistently light up lateral flow tests.”

Because different manufacturers use different reagents in their test kits, some kits may be more susceptible to this problem than others, Edwards suggested. Indeed, many Guardian readers claim to only test positive on certain brands of LFT – particularly FlowFlex kits.

A UKHSA spokesperson said: “All lateral flow devices used by NHS test and trace have gone through rigorous validation and are proven to be highly effective at detecting Covid-19 in those that are infectious.”

Even so, Edwards pointed out that such studies involve testing a certain number of samples under a defined set of conditions: “It does not really reflect the accuracy of the product in real life, and it is not designed to do that.” For any diagnostic test, there are likely to be outliers who produce unusual results: “It could be something as simple as maybe some people have acidic saliva or something like that,” Edwards said.

What to do about it

Petersen stressed that from a public health perspective, such cases are likely to be so rare as to be inconsequential for the overall validity of the tests. “We should remember that millions of people are testing, and on the whole these tests are working, and people should trust the results,” she said.

A UKHSA spokesperson said: “[We] constantly monitor performance of LFDs in use and investigate any issues where appropriate.” They advised people to report any problems with tests via the “give feedback or report harm” section of the gov.uk website.

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