Can Omicron evade detection from PCR and lateral flow tests for Covid-19?

As Omicron causes Covid-19 case numbers around the globe to surge, concerns are being raised over whether lateral flow and polymerase chain reaction tests are able to detect the highly infectious variant.

Lateral flow tests (LFTs), also called rapid antigen tests, have never been the gold standard when it comes to coronavirus testing.

But because they are cheap and give results in about 30 minutes, they are widely used, especially for home testing.

Polymerase chain reaction (PCR) tests are carried out in laboratories and, although more expensive, are typically more sensitive and are less likely to result in a false negative – where a person who is infected is told they are not infected. But there is more to it than that. Here we look at what may be happening with testing and Omicron.

What are the concerns regarding LFTs and Omicron?
Media have reported instances of people repeatedly testing negative on LFTs despite having Covid-19 symptoms, only to test positive later when taking a more sensitive PCR test.

Lateral flow tests use antibodies to detect viral proteins (antigens) in the nasal passages of infected individuals. Their sensitivity is between about 40 per cent and 60 per cent.

PCR tests look for the virus’s genetic material, and involve several cycles of heating and cooling in a machine in which this genetic material is replicated, which helps the tests to be more sensitive.

Because of this difference in sensitivity, the fact that some people have recently repeatedly tested negative with LFTs, only to later test positive with a PCR test, is itself not evidence that LFTs struggle to detect Omicron more than other variants.

“They are less sensitive. It’s quite expected someone that will do a number of lateral flows that will be negative, and then have a positive PCR,” said Paul Hunter, a professor in medicine and an infectious diseases specialist at the University of East Anglia in the UK.

What do officials say about LFTs and Omicron?

In a December 17 briefing document, the UK Health Security Agency said that “initial data” indicated that the LFTs used by the UK Test and Trace service were detecting Omicron.

These tests use two or more different antibodies that recognise distinct parts of the nucleocapsid, which is the protein shell that surrounds the pathogen’s genetic material.

According to the UKHSA document, the nucleocapsid in Omicron has “a single mutational difference from other Sars-CoV-2 variants”.

“As such, the general risk to LFD [lateral flow device] performance being impacted by Omicron was considered low,” the organization said, before adding that further laboratory analysis was being carried out.

A paper published by South African researchers just before Christmas indicated that, with Omicron, mouth swabs are better than nasal swabs at detecting the coronavirus. With Delta, it is the other way round.

As a result, they said that as Omicron becomes dominant, there might have to be a reassessment of the tests used. Their paper has yet to be peer reviewed.

Also, in a statement that went online this week, the US Food and Drug Administration (FDA) said that rapid tests may have lower sensitivity with Omicron.

“Early data suggest that antigen tests do detect the Omicron variant, but may have reduced sensitivity,” the FDA said.

Why might Omicron be showing up less often on LFTs?
Dr Michael Mina, chief science officer of eMed and former associate professor at Harvard University, has offered a possible explanation as to why people with symptoms may be having repeated negative LFTs.

Writing online in mid-December, he suggested that now that many people have been vaccinated or had a previous Covid-19 infection, their immune systems are acting fast when they are infected.

This causes symptoms to develop early, even before viral levels are high enough to be detected by an LFT. Whether this is actually happening, however, is unconfirmed.

Another suggestion – also unconfirmed – is that the Omicron variant is transmitted, and can cause infections, even when levels of the virus in the nasal passages are low and are difficult for an LFT to detect.

If this is the case, it would mean that it is even more crucial that a person isolates when they have Covid-19 symptoms even if their LFT is negative, because they could be infectious.

How much should we rely on lateral flow tests?
Dr Al Edwards, an associate professor in the school of pharmacy at the University of Reading in the UK, said LFTs have always missed some positive cases.

“There may be some differences with the ability of lateral flow tests to pick up the variants, but they never have been able to pick up every case,” he said.

They are, he said, “very, very reliable” as a red flag – meaning that if you test positive, you have the virus and could infect others – but have never been reliable as a green flag, because they cannot confirm that you do not have the virus and are not infectious.

“There’s been advice you should use them before meeting people,” he said. “You should use them, but they can never prove you’re safe."

If a person plans to meet a friend who is not likely to be vulnerable to Covid-19, he indicated that it may be sensible to take an LFT beforehand and to go ahead with the meeting if the result is negative.

On the other hand, if a person is thinking of seeing a person who is more medically vulnerable, such as an elderly relative, they may not want to rely on an LFT in the same way.

Prof Hunter said people with a negative LFT result were “probably not that infectious” because the levels of the virus were likely to be lower.

“Even if they have the virus, they’re probably not shedding a lot, so they’re probably not infectious,” said Dr Edwards.

Can Omicron evade PCR nasal swab tests?
LFTs are not the only tests whose effectiveness in some cases appears to be affected by the emergence of Omicron.

While the WHO said at the end of November that “the widely used PCR tests continue to detect infection, including infection with Omicron”, subsequent analysis has highlighted exceptions.

The FDA identified certain tests that are likely to fail to identify a positive case when the person is infected with Omicron. This is because the part of the virus’s genetic material that these particular tests look for has changed in the new variant.

In an online update released this week, the FDA highlighted a PCR nasal swab test called Revogene Sars-CoV-2, produced by Meridian Bioscience, as “being expected to fail to detect Omicron”.

This is because the test has a single target in the genetic material of the coronavirus, but some of this target has been deleted in Omicron. The FDA recommends that this test not be used until the problem is resolved. The FDA's guidance is specifically for tests for which it issued authorisation.

Another test, produced by Tide Laboratories, had the same issue, but modifications so that there is more than one genetic target mean that it should now detect Omicron.