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A ‘Stealth’ Version of Omicron Could Challenge Surveillance Efforts

A ‘Stealth’ Version of Omicron Could Challenge Surveillance Efforts

A scanning electron microscope image of SARS-CoV-2 (round blue objects) emerging from the surface of cells cultured in the lab. Photo and caption: NIAID/Flickr, CC BY 2.0

  • Since the identification of the omicron variant, scientists from around the world have been sharing its genome data through public sequence repositories.
  • This has helped scientists identify a new sub-lineage that shares most mutations with its parent but lacks one that could render SGTF identification impossible.
  • This could affect surveillance efforts in WHO regions with limited genome-sequencing capabilities, including India, where officials are using TaqPath tests.

There are still considerable uncertainties regarding the new omicron variant (B.1.1.529) thanks to its large number of mutations. This variant likely spreads more easily than the original SARS-CoV2, but its transmissibility compared to the delta variant is not completely known.

The omicron variant seems to be able to cause more reinfections and is expected to evade vaccine-induced immunity. A preliminary laboratory study by Pfizer-BioNTech demonstrated that three doses of their vaccine neutralised the variant whereas two doses couldn’t. Initial data also suggests that the omicron variant causes milder illness compared to the delta variant.

But it is important to be cautious as the epidemiology of disease severity evolves as the outbreak matures and the clinical profile of affected individuals changes.

Data is still emerging, so addressing the unknowns about the variant and preparedness to tackle what it has in store for us depends heavily on our ability to identify and track how the variant is spreading, where and among whom.

The S-gene advantage

The spike protein of the omicron variant is characterised by at least 30 amino acid substitutions, three deletions and one insertion. The variant has been found to include a mutation of the S gene that was first identified in the alpha variant. This mutation causes a dropout of the S-gene target in results from certain PCR tests.

The US FDA has identified 27 tests with the ability to detect this S-gene target failure (SGTF) – of which TaqPath tests from ThermoFisher are being used in India – and thus indicate to clinicians and researchers a possible omicron variant infection without the need for genome-sequencing.

Public health organisations like the WHO and the US Centers for Disease Control have also recommended that clinicians and diagnosticians take advantage of the SGTF to efficiently detect the omicron variant’s presence.

Note, however, that this phenomenon only signals a possible infection with the omicron variant; confirmation requires genome-sequencing.

Emergence of sub lineages

Since the identification of the omicron variant, scientists from around the world have been sharing genomic data through public sequence repositories like NCBI and GISAID. This has helped scientists quickly identify a newly emerging sub-lineage of the omicron variant (denoted BA.2 in the table below). It shares most mutations with its parent but lacks the mutation in the S gene that could render SGTF identification impossible.

Yellow represents mutations unique to the BA.2 sub-lineage, blue represents mutations unique to the ‘original’ BA.1 lineage of the omicron variant and green shows mutations shared by both. The 69-70del mutation in the S-gene has been marked with a pink star. Source:

Implications for health surveillance

The BA.2 sub-lineage lacking SGTF means PCR tests can no longer indicate the presence of the omicron variant. That is, a person infected with the BA.2 sub-lineage will test positive on PCR tests but there won’t be any indication they have the omicron variant.

This could affect surveillance efforts in South Asia and other WHO regions with limited genome-sequencing capabilities. Recently, several states in India, including Maharashtra and Tamil Nadu, have started using TaqPath test kits to screen for the omicron variant among travelers from high-risk areas as part of early detection efforts. This is an effective strategy considering India’s generally limited resources, but the emergence of the BA.2 sub-lineage could render this strategy ineffective.

While testing is a key component in surveillance efforts, it shouldn’t be the only thing determining epidemiological investigation. The following actions must be prioritised in the course of implementing comprehensive surveillance efforts and prioritising genomic sequencing.

* Screen travelers from high risk areas for symptoms suggestive of COVID-19, recent exposure history, immunocompromise, vaccination status and other clinical characteristics – and not just with COVID-19 tests.

* Atypical clinical presentations, outbreaks causing more than expected morbidity and mortality, ‘super-spreader events’, increase in vaccine breakthrough cases and reinfections, clusters with unexpected discordant test results, clusters suggestive of zoonotic transmission, poor response to therapeutics, increase in effective reproductive number and any unexpected trends should alert officials to the possibility of newly emerging variants.

* Pool samples to detect community trends in the transmission of the virus. This is a cost-effective and efficient strategy for rapid detection in changing trends and which could alert us to the variants in circulation.

* Use other surveillance strategies like routine representative sampling, fixed sampling and targeted sampling.

* Improve Environmental surveillance. Viral RNA can be sequenced directly from wastewater and may provide an early glimpse of strains circulating in the community.

* Conduct field epidemiological studies. Enhancing field epidemiological studies to supplement routine surveillance data is key to bridging knowledge gaps. Epidemiological studies of variants are to be prioritised in settings where the population is representative and thus likely to have high degree of generalisability and broad relevance. WHO has developed several standardised generic epidemiological investigation protocols branded as ‘Unity studies’, to promote research and address gaps in current evidence.

* Look out for a sudden increase in the incidence of SGTF results. Prioritise samples since mid-October and any samples that returned results consistent with SGTF for genome-sequencing.

* Conduct broad genomic surveillance to identify the omicron variant. Undertake efforts to improve testing and sequencing capabilities for possible surge in demand.

Lekshmi Rita Venugopal is an epidemiologist with the Idaho Department of Health and Welfare, Idaho.

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