The Untold Story of The Omicron Variants

CME INDIA Presentation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh, India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.

Omicron Variants

Omicron was first reported from South Africa in November 2021 but has since become the dominant variant around the world.

The Omicron variant differs from previous variants of SARS-CoV-2 in the increased number of mutations present in the spike protein (at least 30, including 15 in the receptor binding domain region) relative to previous variants such as Beta (10) and Delta (nine).

Mutations in Omicron are unique and impact

• The performance of certain molecular tests
• Viral transmissibility
• Severity of disease
• Neutralization by monoclonal antibodies or antibodies elicited by covid-19 vaccination or sars-cov-2 natural infection.

Omicron Lineages

• There are several lineages designated “Omicron,” including B.1.1.529, BA.1, BA.1.1, BA.2, BA.3, BA.4 and BA.5.
• The lineage
  • B.1.1.529 includes BA.1 and BA.3;
  • BA.1.1 and BA.2 are categorized separately.

Credit: https://github.com/nextstrain/ncov/pull/984

Preliminary evidence from in vitro studies suggests that immunological protection from BA.1 infection may not protect against BA.4 or BA.5 infection.

• Within the BA.2 lineage, several subvariants have been identified, including BA.2.12, BA.2.12.1 and BA.2.75.
• The subvariants BA.2.12 and BA.2.12.1 are estimated to have an approximately 23%-27% growth advantage above the original BA.2 variant.
• Further Sublineages also continue to occur.

Effects of mutation:

1. S Gene Target Failure:

• The lineages BA.1 and BA.1.1, as well as BA.4 and BA.5, experience S-gene target failure. This led to these lineages being colloquially termed “stealth” variants.

2. At present, there is no evidence suggesting these subvariants cause more severe disease than the original BA.2 lineage.

3. Preliminary evidence about BA.2.75 suggests that, similar to BA.4 and BA.5, its susceptibility to a broad range of monoclonal antibody therapies is reduced.

4. Transmissibility

• Early evidence suggests that the heightened transmissibility of the Omicron variant is not attributable to higher viral loads compared to previous variants but instead to greater immune evasion.

5. Immunity

• Multiple studies have demonstrated reduced neutralization of Omicron by antibodies from vaccinated or convalescent individuals compared with previous SARS-CoV-2 variants.

6. Importantly, booster doses of mRNA and Vector based vaccine appear to restore in vitro neutralization titers in the short term.

7. Severity

• Studies from multiple countries — indicate that infection due to the Omicron variant is associated with less severe disease (decreased risk of hospitalization and death, reduced length of stay, etc.) compared with previous variants of concern, including Delta.

8. Impact on Testing

Omicron cases of all lineages can be detected using RT-PCR in two ways.

• The first is to assess for spike gene target failure in PCR assays. However, BA.2 lineage lacks the mutation that results in spike gene target failure and therefore would not be detected using this method.
• The second way to identify these cases is to use a PCR designed to look for the major mutations specific to the Omicron variant. This method would be able to detect all lineages.
• With respect to rapid antigen tests, three independent studies have shown no change in the analytic sensitivity. But results may vary with tests kit

Recombinant Variants:

• When community transmission levels of virus are high.
• Recombinant viruses can occur because multiple variants infect the same individual at the same time, and the variants exchange genetic material with each other, changing their formulations.   Naming conventions for recombinant variants include an “X,” referring to the intersection of genetic material from two previously distinct lineages.
• There are several recombinant forms of SARS-CoV-2 that involve Omicron genetic material, including
  • XD (Delta-Omicron) and
  • XE (BA.1-BA.2).
• Current evidence suggests that XD is not associated with higher transmissibility or more severe outcomes than its parent strains.

BA.2.75 in India.

Will BA.5 take over India?

• Lineage BA.2.75 / clade 22D has been growing in frequency at a rate of 0.12 per day in India, which is equivalent to initial growth of BA.5 in the US and the UK, and is now outcompeting BA.5 in India.
• These growth dynamics, along with mutational profile, strongly suggest this clade will spread widely, though it may not ultimately displace BA.5 viruses globally.

• The World Health Organisation has classified BA.2.75 as a variant of interest, rather than a variant of concern. This means it’s being monitored but there’s not yet evidence it will cause problems.

CME INDIA Quick Take-Aways

References:

1. https://github.com/nextstrain/ncov/pull/984
2. https://t.co/J4IMw2aVYo
3. https://www.idsociety.org/covid-19-real-time-learning-network/emerging-variants/emerging-covid-19-variants/



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