Are existing rapid antigen tests unable to accurately detect Omicron?

Just seven weeks after the World Health Organization declared Omicron a worrying variant of SARS-CoV-2, the new form of the virus has led to an exponential increase in the number of cases around the world

As scientists gain insight into this new variant, and how mutations in its genome contribute to its transmissibility and pathogenicity, questions have arisen about tests that play a key role in identifying infections

Rapid antigen tests, also known as lateral flow tests (biologics), can detect the viral protein of SARS-CoV-2 in mucus from a person's nose or throat

But controversy has arisen in recent weeks over whether the test can accurately detect the new strain of Omicron

For example, a small study by US researchers this month reported that two widely used rapid antigen tests (Abbott BinaxNOW and Quidel QuickVue) appeared to lag by several days in detecting Omicron cases, although PCR tests from saliva samples ( The results are more accurate, but slower) with a positive result, but the rapid test is still negative

Second, an earlier study published as a preprint by Swiss researchers compared the detection performance of seven SARS-CoV-2 rapid antigen tests against cultured virus (not human samples)

Other groups came to slightly different conclusions, though: A study by one team, published in a preprint of medRxiv on Jan.

The findings are particularly relevant to Abbott BinaxNOW, consistent with those reported in other variant tests, and show that "Omicron does not appear to have any performance deficits," said study co-author Joseph DeRisi of the University of California, et al

Several national organizations have now announced plans for their own investigations

The UK Health Security Agency has tentatively concluded that the rapid antigen tests currently used by the National Health Service show comparable sensitivity to Omicron and other variants, and it continues to monitor them performance

The researchers say it's unclear whether the rapid antigen test actually worked poorly in detecting Omicron cases, or what might have contributed to the discrepancy

As with any diagnostic test, if they're only slightly imperfect, it's not a big deal

Why does Omicron's detection perform poorly?

Although the data are preliminary, scientists and public health experts have proposed hypotheses about why some rapid antigen tests may not perform well for this variant

One possibility the FDA has highlighted is that the devices are less sensitive to this particular form of SARS-CoV-2

While that reason may hold, Edwards said it's unlikely to be a full-blown problem

Another reason the test appears to be less sensitive to Omicron than other variants is whether the amount of virus entering the sample is consistently lower than normal -- in which case fewer samples from people infected with Omicron would contain enough The viral antigen reaches the detection threshold of the device

This could happen, for example, if Omicron replicated previous variants in different parts of the body, so "maybe people weren't taking samples in the right places to test for the virus," says immunologist Gigi Kwik Gronvall
.
According to this hypothesis, it is possible that "more virus can be obtained from saliva or throat swabs" compared to nasal swabs
.

Several studies support this view
.
For example, some researchers believe that a U.
S.
study this month comparing rapid antigen tests and PCR saliva tests showed that throat swabs could pick up more cases
.
Another preprint by South African researchers found that PCR tests were more able to detect positive cases in throat swabs than in nasal swabs
.
But Edwards cautioned that there are uncertainties in these comparisons, and he is waiting for more data before drawing conclusions about whether the swab location may have contributed to a significant difference in the performance of the Omicron test
.

Another possibility, Gronvall noted, has to do with Omicron's apparent ability to replicate, at least in some tissues, at a much faster rate than previous variants, meaning that negative results are informative in less time
.
In other words, "people go from below the test threshold to positive much faster than for Delta virus
.
" This may explain some studies reporting that "people are spreading the virus before they test positive
.
"

Scientists studying Omicron's transmission biology also discussed whether reports of reduced detection performance are actually related to potential differences in Omicron's infectivity from previous versions of SARS-CoV-2
.
For example, a variant that is infectious at low doses may be associated with a higher false-negative rate in an infectious population
.

Molecular and virological research into the spread of the Omicron virus is still in its early stages, but several preprints published in the past few weeks suggest that there may be relevant differences in how and where the Omicron virus infects human tissues
.
For example, Ravindra Gupta, professor of clinical microbiology at the University of Cambridge, and colleagues found that Omicron appeared to no longer infect pre-sars-cov-2 target cells, those with ACE2 and TMPRSS2 proteins on their surface.
cells
.
While Omicron still requires ACE2, it is now much better at entering cells with little or no TMPRSS2
.

The change, which the team reported in a preprint a few weeks ago, could explain the observation that Omicron tends to be more present in the upper airways, such as the nose and throat, than deep in the lungs
.
The virus can also be made more easily spread by increasing the amount someone releases when they talk or cough, Gupta noted
.
He added that some preliminary data also suggested that Omicron increased binding affinity for the ACE2 protein (although this finding was not consistent among the research groups), which could lead to higher infectivity and could mean that smaller amounts of ACE2 are needed.
virus to infect another person
.

Molecular virologist Joe Grove of the MRC University of Glasgow Centre for Virus Research and colleagues also investigated how Omicron infection differs from previous variants at the cellular level
.
They report in a recent preprint that reduced reliance on TMPRSS2 appears to be related to a shift in the cell-entry machinery: while earlier versions of SARS-CoV-2 used TMPRSS2 to fuse with the cell membrane and inject its contents, Omicron favored the virus being A TMPRSS2-independent endocytic pathway of phagocytosis
.

Grove speculates that work by other groups also hints at this shift, which could make Omicron a more stable and therefore potentially more infectious virus than previous variants
.
For viruses in general, "cell surface fusion usually requires the virus to have a one-trigger, two-trigger trigger, so it's easier to trigger fusion, which is good for cell entry, but not good for stabilization," despite now saying this general trend Whether it will affect the transmission of SARS-CoV-2 is too early
.

In explaining possible differences in the Omicron test, the researchers have not yet separated these hypotheses from others, nor have they excluded confounding factors that complicate the comparison of Omicron with the previous variant—for example, while the previous variant was in most of the Spread among susceptible populations, many people now infected with Omicron have been vaccinated and/or infected with previous variants
.

"There are a lot of ideas and a lot of potential hypotheses, but the reality is that we need to do these studies to figure it out
.
"

Should people change their behavior?

Even without a clear explanation for what happened with the Omicron test, some countries have reacted to recent research by suggesting that people change the way they use the rapid antigen test
.

For example, according to Reuters, the Israeli Ministry of Health advised people to wipe their nose and throat with cotton swabs
.
Several researchers in the United States have discussed the same approach, potentially improving the chances that tests will find enough virus
.
(Some countries, such as the UK, have approved devices for processing throat and nasal samples
.
)

The researchers say there is a lack of evidence that the practice is beneficial
.
"I think there's more media coverage than we know about what's going on in the larynx," Gronvall said,
adding that using this method for a nasal swab-only test is clearly not FDA-approved method
.
While the combined use of throat and nasal swabs (rapid antigen tests) "would be surprising if it didn't work", more research is needed to show whether it has an impact on test performance
.

The U.
S.
Food and Drug Administration (FDA) itself opposes the practice, tweeting: "Currently available at-home antigen tests are only authorized to use nasal swabs
.
We don't have any data yet to suggest that throat swabs are a an accurate or appropriate home testing method
.
”

Most importantly, people should remember that no test is perfect, the researchers stressed: a negative result does not guarantee that a person is not infected with SARS-CoV-2 or that they cannot infect others
.
Individual COVID-19 cases vary widely, with different people producing and transmitting different amounts of the virus at different times after infection
.
He argues that "rapid tests are not a good way to test for infectivity" and that there is no test, PCR or otherwise, at the individual level that can prove you're not infectious
.
"

Gronvall advises people to "consider when you may have been exposed to the virus - if you have symptoms but haven't tested positive, you may have had the virus and you need to be retested in a few days,
" she added.
People should also remember that testing needs to be combined with immunizations and other health measures to help stop the spread of COVID-19, he said
.

Edwards agrees that testing is only part of the fight against COVID-19, saying he is not concerned about small variations in the performance of tests for different variants
.
"My only concern is whether people are led to believe that [rapid antigen tests] are perfect when in fact they are not, or whether people think, because they are not perfect, they shouldn't bother
.
Those two extremes are Very harmful -- at one extreme is saying, 'Okay, I've had my test, I know I'm negative, and I can do whatever I like,' and at the other extreme, saying, 'Okay, I'm not going to take the time to do these tests because they're not accurate
.
'"

(Catherine Offord/Biology Compilation)