Omicron Coronavirus variant
Discovery
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Rhiannon Jenkinson, PhD

Omicron: The Latest SARS-CoV-2 Variant on the Block

What should we make of this new COVID strain, which has circled the globe in a matter of weeks?

The SARS-Cov2 virus that causes COVID-19 is constantly evolving and mutating. It changes its nucleic acid sequence, which in turn changes the protein building blocks that the virus is made up from. To enable new variants of the virus to be easily named rather than using complex scientific nomenclature the world health organisation implemented a system using Greek letters (1). Omicron is the 15th letter of the Greek alphabet and is the name of SARS-CoV-2 variant of concern (VOC) B.1.1.529 that has everyone on edge (2). Is it the variant to end all existing variants, or will its predecessor, the Delta variant, remain the dominant one in circulation? This primer addresses some of the major questions around Omicron, beginning with this handy chart that describes what a variant of concern is and how they are classified.

VOI (variant of interest) definition

VOC (variant of concern) definition

A SARSCoV2 variant with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, disease severity, immune escape, diagnostic or therapeutic escape; AND

SARSCov2 variant that meets the definition of a VOI and has been demonstrated to be associated with one or more of the following changes that could have global public health significance.

Identified to cause significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence alongside increasing number of cases over time, or other apparent epidemiological impacts to suggest an emerging risk to global public health. 

Increase in transmissibility or detrimental change in COVID-19 epidemiology; OR

 

Increase in virulence or change in clinical disease presentation; OR

 

Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

Table generated from WHO definitions (3).

How is Omicron different from other SARS-CoV-2 variants and why are scientists and politicians worried about these changes?

Omicron was first reported in November in Botswana, Africa where scientists sequenced the virus as part of a diagnostic and surveillance program for detecting SARS-CoV-2 (4). This allowed timely tracking of Omicron to occur across the world and for scientists to start work on understanding the implications of this variant to public health and vaccine strategies. The mutations found in Omicron were in several parts of the virus (5) but perhaps the most immediately concerning were the 30-plus mutations found in the spike region of the virus.

The spike protein of SARS-CoV-2 binds to the ACE2 receptor which is present on some cells in our body, allowing the virus to enter and infect these cells. Changes to the spike protein have a few worrying potential implications.

Why should we be concerned if the spike protein is mutated?

The spike protein of SARS-CoV-2 binds to the ACE2 receptor which is present on some cells in our body, allowing the virus to enter and infect these cells. Changes to the spike protein have a few worrying potential implications.

  • It may allow better binding of the virus to ACE2 resulting in better or more efficient entry of the virus into our cells. This could impact on the severity of disease.
  • It could lead to higher transmissibility, and ultimately an increase in the ability of the virus to spread between individuals. 
  • It could lead to immune evasion; all current licensed vaccines in the European Union and US have been developed using the spike from the original Wuhan SARS-CoV-2 variant. The antibodies we have generated via vaccination bind the viral spike and prevent or limit SARS-COV-2 viral entry into our cells.  The worry now is that as the spike sequence changes these antibodies may no longer bind as effectively to neutralise the virus.  However, it is important to note that vaccines do not just drive antibody responses, they activate our CD8 T cells; the role of these ‘killer’ or cytotoxic cells is to target SARS-CoV-2-infected cells and kill them.  T cells are exquisitely specific with each T cell receptor (TCR), recognising a specific fragment of protein (peptide) presented to it by our major histocompatibility protein I (MHCI), present on most cell types.  As many CD8 T cells recognise small fragments of protein mutations in the spike are less likely to impact T cell responses.

What is the data suggesting that the Omicron variant may act differently and therefore pose a greater risk to public health?

We still have a lot to learn about the Omicron variant, but scientists’ findings are being reported and published quickly. Still, many reports need to be peer-reviewed. What we do know so far is that the Omicron variant appears to be spreading quickly and may quickly become the dominant variant. Yet we still don’t have enough data to know if infection with Omicron will lead to severe disease and increased hospitalisation in the unvaccinated and the amount of protection that vaccinated individuals will have.  Initial data points to Omicron having a higher R rate of 3-5 than the currently dominant delta strain of 1.1-2.2, which means that one individual infected with the Omicron variant could pass the virus on to between 3-5 individuals leading to a quick and potentially massive increase in the number of people infected.

Which begs the question, with a variant this transmissible will our stockpile of vaccines protect us? And does infection by a different variant make us immune to Omicron?  Initial studies using neutralising antibody studies indicate that vaccines or previous infection from other variants give us limited antibody protection against Omicron, though the extent of protection  varies depending upon which vaccine we received (6).  Early data indicates that boosting enhances protection and vaccine effectiveness by as much as 70-75%, at least in the early period following the booster shot (7-9).  This has led countries, such as the UK, to administer RNA vaccine boosters to as many people as possible (10.)  It is hoped that this strategy will limit severe disease and hospitalisations, although it is possible that mild disease cases may not be impacted.  The coming weeks will tell us more.

One hope for the Omicron strain is that it may lead to milder disease and be more like the endemic coronavirus strains such as 229E which commonly circulate amongst us and are a cause of the common cold. Yet we have no clear data to support this hypothesis. Data coming out of South Africa from their largest private health insurer (11) suggests that Omicron is spreading faster than previous variants but that the risk of hospitalisation is 29% lower than in the previous wave of Delta variant cases, and risk of progression to severe disease is reduced. In terms of vaccine effectiveness, they examined the Pfizer/BioNTech RNA vaccine and found that it provided only 33% protection compared to the previous 80% protection against the Delta variant.  On a more positive note, however protection against severe symptoms requiring hospital admission was not as reduced—70% for Omicron compared to 93% for Delta. Re-infections were also significantly higher for Omicron than observed for other variants, indicating that natural immunity to infection with other COVID-19 variants did not always confer protection to re-infection with Omicron.  The age demographic in the South Africa population and high levels of SARS-CoV-2 antibodies in the general South African population following an extensive wave of Delta infections, could mean that the impact of Omicron may differ in other countries.

In the meantime, many countries are scaling up non-pharmaceutical measures, such as social distancing, mask wearing, encouraging hygiene precautions, and bringing in vaccine passports and enhanced surveillance through PCR and lateral flow testing, to reduce the spread of COVID.  It is hoped that these may slow down the spread of Omicron until we understand better how to control its spread and develop boosters that are more effective against Omicron.

Useful Definitions:

Transmissibility: the ability of the virus to spread between individuals

Epidemiology: The study of how often diseases occur in different groups of people and why.

Virulence: measurement of the degree of damage a micro-organism is likely to cause to the infected individual or host.

Clinical disease presentation: The symptoms that people have as a consequence of infection.

Diagnostics: how we detect that people are infected with the virus (eg PCR test, Lateral flow test).

Vaccines: a preparation that is used to stimulate the body’s immune response against diseases

Therapeutics: drugs or medicines used to prevent or limit infection such as anti-virals or drugs or medicines used to treat the effects of viral infections such as immunomodulators (eg dexamethasone, IL-6 blockers)

Bibliography

1.  WHO announces simple, easy-to-say labels for SARS-CoV-2 Variants of Interest and Concern. https://www.who.int/news/item/31-05-2021-who-announces-simple-easy-to-say-labels-for-sars-cov-2-variants-of-interest-and-concern.

2.  SARS-CoV-2 variants of concern as of 14 December 2021. European Centre for Disease Prevention and Control https://www.ecdc.europa.eu/en/covid-19/variants-concern.

3.  Tracking SARS-CoV-2 variants. https://www.who.int/emergencies/what-we-do/tracking-SARS-CoV-2-variants.

4.  GISAID - Initiative. https://www.gisaid.org/.

5.  CoVariants. https://covariants.org/.

6.  Dejnirattisai, W. et al. Reduced neutralisation of SARS-COV-2 Omicron-B.1.1.529 variant by post-immunisation serum. 2021.12.10.21267534 https://www.medrxiv.org/content/10.1101/2021.12.10.21267534v1 (2021) doi:10.1101/2021.12.10.21267534.

7.  Garcia-Beltran, W. F. et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. http://medrxiv.org/lookup/doi/10.1101/2021.12.14.21267755 (2021) doi:10.1101/2021.12.14.21267755.

8.  Pfizer and BioNTech Provide Update on Omicron Variant | Pfizer. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant.

9. Doria-Rose, N. et al. Booster of mRNA-1273 Vaccine Reduces SARS-CoV-2 Omicron Escape from Neutralizing Antibodies. 2021.12.15.21267805 https://www.medrxiv.org/content/10.1101/2021.12.15.21267805v1 (2021) doi:10.1101/2021.12.15.21267805.

10. SARS-CoV-2 variants of concern and variants under investigation. 42.

11. News room | Discovery - Discovery. https://www.discovery.co.za/corporate/news-room.