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Genomic structure and important mutations seen in the Omicron Variant of the SARS-COV-2 virus. Source: Stanford HIVDB Team - https://covdb. stanford.edu/page/mutation-viewer/, CC BY-SA 4.0
Beyond the S-protein, the Delta 105-107 mutation seen in the N-terminal region could aid innate immune evasion by com- promising the host cell’s ability to degrade viral components. In addition, the R203K, G204R mutations have been linked to sub-RNA expression and increased viral loads in the nucleo- capsid region. Lastly, an insertion mutation (ins214EPE) has been detected in this variant of SARS-CoV-2. Interestingly, while ins214EPE has never been seen in SARS-CoV-2,
it is known to occur in another common cold corona- virus, HCoV229E. It is postulated that the genomes of HCoV229E and SARS-CoV-2 interacted in a co-infected individual and may have contributed to the development of the Omicron variant.
Sub-lineages, S-gene target failure
(SGTF), and the ‘Stealth’ variant
Omicron global phylogeny shows the continued evo- lution and divergence into sub-lineages. The Omicron variant has three major sub-lineages, BA.1, BA.2, and BA.3. First detected in South Africa, the BA.1 sub-lin- eage has the typical Omicron mutations and was the sub-lineage that displaced the Delta variant. The BA.2 lineage has 28 additional mutations. The BA.2 lineage arose around the same time as the BA.1 lineage and the earliest cases were detected in East Asia. By early Janu- ary, BA.2 sub-lineage had was seen worldwide, partic- ularly in Denmark and the United Kingdom. The BA.3 sub-lineage has not been widely reported.
SGTF is defined as a PCR test where the N and ORF1ab genes are detected, but the S gene is not. Unlike the Delta variant, the BA.1 sub-lineage is associated with a deletion mutation S69/70 that causes an S gene target failure (or SGTF) in specific PCR reactions. Therefore, in certain parts of the world, SGTF rates were used to track the replacement of the Delta variant by the Omicron variant, most of which were of the B.1 sub-lineage.
The BA.2 sub-lineage has been incorrectly termed the ‘stealth variant’in lay media. While the word ‘stealth’ suggests that BA.2 will not be detected by PCR reactions, the reality is that all variants and subvariants of SARS-COV-2 are detected by PCR reaction. At this point, RT-PCR methods remain sensitive and specific because they use multiple genetic targets to detect the SARS-COV-2 variants. So what is the source of this confusing term? As discussed earlier, the BA.2 sub-lineage of Omicron lacks SGTF. Therefore, if the BA.2 sub-lineage starts to replace the BA.1 variant, SGTF rates can no longer be used as a proxy marker to track the replacement of the delta variant by the BA.2
sub-lineage, ergo the intent behind using the term ‘stealth’, albeit incorrectly. This ‘stealth’ phenomenon may not be a significant concern since the Omicron variant’s sub-lineages already consti- tute >95 percent of newly detected cases in the United States.
Figure shows the replacement of the Delta variant by the Omi- cron variant in Michigan in late 2021 and early 2022. Source: www.outbreak.info
12 Detroit Medical News
First Quarter 2022
Figure shows the replacement of the Delta variant by the Omicron variant in Michigan in late 2021 and early 2022. Source: www.outbreak.info
Omicron Pathophysiology
In mid-December of 2021, the United Kingdom Health Secu- rity Agency (UKHSA) reported that the Omicron variant has a transmission advantage compared to the Delta variant. While the Delta variant took more than 50 days (about one and a
half months) for the first 5000 cases in the United Kingdom, the Omicron variant reached the same number around ten days (about one and a half weeks). According to UKHSA, the household transmission risk of the Omicron variant is high – the adjusted odds ratio for household transmission from an Omicron index case was 2.9 compared to Delta index cases. UKHSA’s s analysis suggested that the risk of reinfection with the Omicron variant may be about three times higher than the risk of reinfection with other SARS-COV-2 variants. Further, UKHSA showed that vaccine effectiveness against symptomatic disease with the Omicron variant is significantly lower than the