Scientists are calling for an urgent investigation after dozens of reports of people testing negative using gold-standard Covid PCR tests, despite testing positive on rapid lateral flow tests, and in many cases experiencing Covid-like symptoms.

The UK Health Security Agency (UKHSA) said it had been made aware of people in some areas of the country anecdotally reporting positive lateral flow test results with subsequent negative PCR tests, and that it was looking into the cause.

Scientists told the Guardian that they would like to see more being done to ensure that members of the public who may be infected with the virus are not being falsely reassured that it is safe for them to mix with other people.

Alan McNally, a professor of microbial evolutionary genomics at the University of Birmingham, who helped establish some of the Lighthouse labs, state-funded Covid-19 testing facilities, said: “There needs to be really clear and immediate messaging from government around which test [people should] act on. My very clear advice would be that if you have a respiratory infection, stay at home because you’re going to pass it on.

“But if you’ve got symptoms of a respiratory infection and a lateral flow test that’s positive, I would be working on the assumption that it’s Covid-19 regardless of the PCR result at the moment. That message needs to be made clear, which then buys time for the Department of Health and UKHSA to do a quality audit of the PCR testing process and try to find out where the issue may be.”

Dr Kit Yates, a senior lecturer in mathematics at the University of Bath said: “I would suggest that this is investigated with the utmost urgency. In the meantime, people testing positive on lateral flow devices (LFDs) should isolate if they can. A further independent positive LFD test will help to confirm the Covid-positive diagnosis, despite a negative PCR test. The lack of ability to claim [financial] support for isolation without a positive PCR test further emphasises the need for the urgent resolution to the problem.”

Anecdotal reports have suggested that the issue may be more widespread in south-west England, prompting speculation that a new variant of Sars-CoV-2 may be the cause. However, GPs in Manchester and Oxfordshire have also reported discrepancies between lateral flow and PCR test results, and scientists think a new variant is unlikely.

McNally said: “The vast majority of PCR tests that are done in the UK target three parts of the viral genome, and the idea that a new variant would come up where all three targets fall out just isn’t going to happen. There’s also still an enormous level of genome surveillance going on, which would have picked this up.”

The UK Health Security Agency also said that there is no evidence for the emergence of a new variant, and that existing variants have been tested against the LFDs in use, which continue to work at the expected standards.

Although no Covid-19 test is 100% accurate, the number of cases being reported suggests that something else may be going on. “I don’t think that the maths explains all of these cases. Especially what’s going on in the south-west, and in particular cases where there are multiple LFD positives followed by multiple PCR negatives,” said Yates.

Prof Oliver Johnson, director of the University of Bristol’s Institute of Statistical Science, said: “The key thing for me is that the proportion of LFTs that passed PCR retesting (where an individual’s LFT is confirmed by a PCR test) dropped in last week’s test and trace report, when it really shouldn’t have done, given the prevalence [of the virus.]”

Another theory is that lateral flow tests, which detect a coronavirus protein called nucleoprotein, are mistakenly reacting against nucleoprotein from a different seasonal coronavirus. Though possible, this is also considered unlikely.

Rupert Beale, who runs the Cell Biology of Infection lab at the Francis Crick Institute in London, said: “There’s extensive potential cross-reactivity with seasonal coronaviruses, but at least in the UK they’re tested for this against three of the four seasonal coronaviruses.”

The fourth, HKU1, has not been tested because it is difficult to grow this virus in the lab. Although it can trigger common cold symptoms, including shortness of breath, cough and a runny nose, other Covid-like symptoms are less common, although fever and chest pain, and gastrointestinal symptoms, do sometimes occur.

Even so, McNally believes another explanation is more likely: “If we rule out a new strain and we rule out cross-reactivity, that points to something within the PCR testing process. It could be anywhere from the swab being taken, to the test being done, to the result being disseminated.

“I would hope that someone is looking on a lab-by-lab basis at the results and the data that they are producing.”

Susan Hopkins, the chief medical adviser at the UKHSA, said: “If you get a positive LFD test, it’s important to make sure that you then get a follow-up PCR test to confirm you have Covid-19. If you have symptoms of Covid-19, self-isolate and take a PCR test. With any test, it is important to carefully read and follow the instructions for use on the test kit so as to avoid any incorrect readings.”