Why some PCR results are negative after a positive lateral flow test

The government’s health agency is investigating a rapid rise in negative Covid-19 results from a PCR following a positive lateral flow test among schoolchildren.

The proportion of pupils testing positive on a home Covid-19 kit and then getting “the apparent all-clear” by the “gold-standard” PCR has almost doubled, reported Tom Whipple, science editor at The Times.

The UK Health Security Agency, formerly Public Health England, said it was aware of the problem and is looking into the cause, but does not yet have an explanation as it has “not experienced this before to such a degree”, said The Telegraph.

Out of 14,000 secondary school children in England whose lateral flow tests (LFTs) were positive in the third week of September, 7% (957) turned out to be negative in a laboratory PCR. This proportion rose to 12.5% (2,000 out of 16,000) the following week.

One GP in Bristol said on Twitter that her son had “lit up” lateral flow tests “like the Blackpool lights” but had a negative PCR result, while another parent in Cheltenham estimated that this had happened to around 12 children in her son’s class after they had “horrible fluey colds”.

The i news site collated anecdotal reports of people testing positive on multiple lateral flows before testing negative on multiple PCRs.

A number of unproven theories have been put forward, from a faulty batch of LFTs or a new variant of Covid undetectable by PCRs to different swabbing techniques and children faking positive lateral flow results.

GP Online said the UK Health Security Agency had ruled out the possibility of a new variant as the cause and said that there was no evidence of “technical issues” with PCR testing kits. The agency’s chief medical adviser Susan Hopkins did, however, urge the public to “carefully read and follow the instructions for use on the test kit so as to avoid any incorrect readings”.

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Writing on The Conversation, Christian Yates, senior lecturer in mathematical biology at the University of Bath, offered another potential explanation. While LFTs do not give many false positives and PCRs do not give many false negatives, neither are 100% accurate, and these anomalies “can add up” when lots of people are taking tests, explained Yates. 

In March, the government estimated that there would be fewer than one false positive in every 1,000 LFTs carried out, while PCR tests have a false negative rate of 5%.

So “if you test positive on an LFT, the overwhelming likelihood is that you have Covid”, said Yates, author of The Maths of Life and Death. And as the prevalence of Covid-19 in a community increases, these “surprising” testing sequences are more likely to occur, he added.

Whipple argued that the latest “large jump in negatives” is unexpected, as it has come “without an apparent corresponding change in prevalence” and the number of discrepancies are higher than what might be expected.

Some questioned whether “other sniffles and colds” could perhaps raise the false positive rate in lateral flow tests, he added.

Catherine Moore, consultant clinical scientist in virology for Public Health Wales, said that lateral flow tests rely on “non-viscous liquids” from the nose, but in the cold and flu season the nose becomes distinctly more viscous. She suggested false positive results might therefore be associated with higher mucus levels.


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