Dive Brief:

• FDA on Friday published a list of molecular tests for COVID-19 that may be affected by mutations in the omicron variant of concern that continues to spread across the globe.
• The agency's list focuses on coronavirus tests impacted by S-gene drop out, an occurrence that is most commonly associated with Thermo Fisher Scientific's TaqPath test kits. When TaqPath is used on a variant with a deletion in the spike gene, such as alpha and omicron, it only detects two of the three target genes.
• Since the S-gene is detectable in the dominant delta variant, FDA is asking laboratories that have "access to quick turnaround whole genome sequencing services" to consider sequencing samples that are affected by dropout. Thermo Fisher has already hailed its test as having an "S-gene advantage" that may help with early identification of omicron. While the S-gene dropout may provide a "signal" that omicron is present, FDA reiterated that the presence of the pattern does not mean an individual with SARS-CoV-2 has omicron. 

Dive Insight:

S-gene dropout first emerged on the radars of regulators as the alpha variant spread at the start of the year. At that time, S-gene dropout enabled researchers to roughly track the displacement of other SARS-CoV-2 viruses by alpha by looking at increases in the rate of tests delivering positives on some but not all target genes.

As delta has an S-gene that is detectable by tests such as TaqPath, the fall in the rate of S-gene drop out showed how that variant steadily replaced alpha. Now, the same data may show the rate at which omicron replaces delta and enable the targeted sequencing of samples to confirm they are the new variant.

The approach is only viable with tests that check for multiple genes. If a test only checked for the S-gene, it would deliver a negative result when used on a sample containing alpha or omicron.

FDA has identified 26 molecular tests affected by S-gene dropout. The best known tests on the list are three versions of TaqPath from Thermo Fisher.

TaqPath laboratories handle around one-third of all specimens tested in England, putting the test at the heart of the effort to track the changes from alpha to delta to omicron. With Thermo Fisher generating more than $1.5 billion from COVID-19 testing in the third quarter alone, TaqPath is likely to be widely used in other markets as well. 

The other 23 tests listed by FDA include a product from Verily Life Sciences. Like TaqPath, the Verily product tests for three parts of the SARS-CoV-2 genome, meaning it can deliver a positive result by identifying the ORF1ab region and nucleocapsid gene even if there is a deletion in the S-gene. FDA is asking clinical laboratory staff and healthcare providers to be aware that S-gene dropout is consistent with omicron but is not recommending changes beyond targeted sequencing, if possible.

While the available tests detect omicron, developers are working on products specific to the variant. TIB Molbiol, which Roche recently acquired, has developed three research-use test kits that are designed to detect omicron mutations. The kits run on LightCycler and cobas z 480 analyzers. Roche said the tests can help researchers "with improved variant detection and viral research."

The tests are for research use only. Roche has assessed all its PCR tests against the publicly available omicron sequences and found they all correctly identify the new variant.

Makers of both PCR and rapid antigen tests have said their tests can detect omicron. FDA on Nov. 30 said that it appears likely that most widely used tests in the U.S. should detect the variant, according to its preliminary review.