DH Deciphers | Can an RT-PCR test detect Omicron?

The heavily mutated Covid variant Omicron has shown signs that some RT-PCR test kits may not be able to detect it. But this strength of the virus could also be its Achilles' heel because it could potentially mean that some other RT-PCR test kits could be capable of detecting who has been infected with this new variant. And any early detection of Omicron during the testing stage could serve as an advance warning and help in containing the virus. Here's more on it: 

Which current RT-PCR testing kits have a problem detecting Omicron?

The RT-PCR kits use a combination of two or more primers to target the nucleic acid of the virus at two more genes or sites. The novel coronavirus has several genes: M, N, E, ORF1a, ORF1b and S (which encodes the spike protein). (The spike protein is the virus’ protruded area that helps it enter the human body.) Omicron’s spike protein is said to have become severely mutated. Therefore, kits that use a primer that's coded to detect the S-gene could deliver a negative result, said Dr Gautam Wankhede, Director, Medical Affairs, Mylab Discovery Solutions, which manufactures test kits.

How serious is the problem?

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According to Dr Benazir Fathima, founder and chief scientist of Azooka Labs, which is also involved in developing RT-PCR test kits, in silico (computer) analysis of an Omicron S-gene found that most RT-PCR test kits can detect the virus but there may be some degree of detection error. “Not all kits will fail. The problem is more acute in RAT tests, which may not work well,” she said. 

Is this a problem for Karnataka?

Yes, this has implications for the state, which has used the RAT for about 25% of its testing in the last 14 days. On November 29 and 30, RAT was used in 47% and 30% of the tests, respectively.

Has this not been seen before?

According to scientific literature, spike protein mutations have been noted in other variants — notably the Alpha, which have also served to deliver false-negative results from the kits. Dr Experts, however, note that this is not generally a problem because RT-PCR tests have at least two primers designed to examine two different genes and the second primer can detect the virus and deliver a positive result. However, he added that even a failure to detect the S-gene, a phenomenon known as the Spike Gene Target Failure (SGTF), could be advantageous. 

Advantageous, how?

The SGTF can actually serve as a proxy to allow us to screen for specific variants. For example, the World Health Organisation (WHO) said that test kits such as Thermo Fisher’s TaqPath Assay, which has three different primers targeting three different genes (N, S and E), can be used as a marker for Omicron. This is because if this test does not detect the S-gene but nevertheless provides a positive result through the detection of the N or the E genes, this means that the infected person was likely affected by the Omicron. By the same logic, RT-PCR kits which do not use a primer for the S-gene will not be useful for screening. 

Is this enough of a confirmation?

No, confirmation must ultimately be made through genome sequencing, but a positive result of Omicron from RT-PCR serves as an advanced warning.

How sure are we of all this?

Dr Wankhede points out that further clarity on the effectiveness of test kits can only happen after actual S-genes from the virus are studied.