Investigating the Omicron variant, part 1: what we know so far

Written by: Rosie Lobley and Ben Caldwell

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In late November 2021 the Omicron variant, a new form of SARS-CoV-2, began to trigger growing concern among researchers and medical professionals, due to its unprecedented rate of infection and heightened ability to evade existing antibodies. In the first of a two-part series on Omicron, following our deep dive on the Delta variant, we examine the available data to determine what we know so far about the Omicron variant, what we do not yet know, and what might happen next.

Omicron variant
Data from Nextstrain.org; image adapted from Kupferschmidt K. Science 2021;354(6572):1179 . Available at: https://doi.org/10.1126/science.acx9754.

How do new variants of SARS-CoV-2 develop?

Viruses constantly mutate due to small errors in RNA replication during virus reproduction. Mutations commonly make little difference to the virus’s survival and behaviour, but rarely they may improve the virus’s fitness (survivability) or make it somehow worse. Through the evolutionary principles governing all life on earth, variants with mutations that improve their chances of surviving and replicating tend to become more dominant in the population.1 The ‘immense’ number of COVID-19 cases around the world has resulted in increased opportunities for the virus to mutate, evolve and develop new variants.2

What sets Omicron apart from other variants?

Variant B.1.1.529 of the SARS-CoV-2 virus – the ‘Omicron’ variant – appears to have mutated in parallel with earlier variants, rather than evolving from them. As of December 2021, researchers believe it may have undergone extensive mutations under selection pressure in a chronically infected, immunosuppressed patient. Alternative theories posit that the variant may have arisen following a reverse zoonotic event, in which the virus jumped into an animal species then back again,3 or may have evolved through exposure to the mutagenic drug molnupiravir, which is used as an antiviral agent and induces errors in the genetic code of a virus as it replicates.4 Omicron was first identified as a Variant of Concern – a mutation which is more transmissible, more severe or more resistant to vaccination or treatment than other variants – on 26 November 2021, following the collection of the first confirmed specimen of the variant on 9 November.5

The Omicron variant has between 20 and 35 mutations to the protruding spike proteins, which enable the virus to attach itself to host cells and which are the main part of the virus targeted by antibodies and vaccines (by comparison, the Delta variant had fewer than 15 spike protein mutations).3 Several of the mutations seen in Omicron are specifically associated with transmissibility, immune escape (the ability of a virus to bypass the host’s immune system) and viral binding affinity (the virus’s capacity to cling to host cells).6 This appears to mean that the new variant spreads much more quickly and in more vaccinated and previously infected patients than previous variants7. Modelling data suggests that a combination of mutations concerning immune escape and heightened transmissibility would be most likely to exacerbate the pandemic.8

Omicron variant spike protein

Why has the emergence of Omicron triggered such concern?

Case numbers are increasing exponentially; the Omicron variant is three to six times as infectious as the Delta variant,9 while patients who have previously been infected with the virus are five to six times more likely to be reinfected with Omicron than with Delta.7 The spread of the Omicron variant has been markedly swifter than that of its predecessors: the Delta variant, which was responsible for 6% of COVID-19 cases on 29 March 2021, grew to make up 75% of cases by 28 September; by comparison, Omicron was responsible for 96% of cases by 21 December, just three months after it was first identified.10

Early evidence in specific populations11 indicates that Omicron is associated with a reduction in the risk of hospitalisation compared with formerly dominant variants.12 However, projections based on the Omicron variant’s rapid rate of transmission and ability to bypass host antibodies suggest that the sheer scale of its spread will result in proportionally greater numbers of hospitalisations and deaths than the Delta variant.13 Indeed, UK-centred modelling suggests that in a ‘worst case’ scenario featuring high rates of immune escape by the virus and low efficacy of booster vaccine doses, hospitalisations could reach double the peak seen in January 2021.14

Data from NextStrain.org.

Will current vaccines still be effective against the Omicron variant?

Antibodies from patients who have received two doses of the vaccine are markedly less effective at neutralising Omicron than previous variants,15 possibly owing to the high number of mutations observed in the omicron variant.6 To date, patients who have been vaccinated against COVID-19 appear to be experiencing less severe symptoms than unvaccinated patients.16 Furthermore, patients who have received a third ‘booster’ dose show greatly improved levels of protection.17

While the Omicron variant has shown some capacity to evade the antibodies produced by patients who have been vaccinated or who have been previously infected, it appears to remain vulnerable to T-cells: white blood cells capable of identifying viral fragments and destroying infected cells before the infection can spread.18 Preliminary research suggests that up to 70% of the T-cell response engendered by vaccines is maintained against the Omicron variant.19

How far has the Omicron variant spread around the world?

On 14 December, World Health Organization (WHO) Director General Dr Tedros Adhanom Ghebreyesus indicated that cases of the Omicron variant had been confirmed in at least 77 countries around the world, and that the variant is probably already present in most other countries but has not yet been detected.20 By 16 December, the European Centre for Disease Prevention and Control (ECDC) reported that 85 countries had confirmed cases.21 Spikes in cases in Europe,22 the US23 and Australia24 are triggering the reintroduction of restrictions such as social distancing and compulsory mask-wearing, as well as the accelerated rollout of vaccine booster doses.

What is going to happen next?

While intense research continues into the risks and strategic implications of the Omicron variant, we may not be able to gain a clear picture of the exact threat it poses for some weeks.25 Modelling in the UK10 and Europe12 suggests that cases will continue to grow exponentially and at pace, and Omicron has already become the dominant strain of SARS-CoV-2 in England, the US and South Africa in the space of just a few months.26 The continued rollout of vaccines and boosters is an essential step in ameliorating the potential harm caused by the Omicron variant, both in terms of lowering transmissibility and – crucially – lowering the risk of severe and long-term symptoms.27

There remains a great deal of uncertainty surrounding the Omicron variant, its origins and its implications for the future, both in the short and long term. As more data becomes available, we will continue to provide updated, evidence-driven reports on COVID-19 variants, vaccines and treatments. In 2022, once more data has become available, we will launch the second part of our Omicron feature, highlighting and analysing new and updated information. Look out too for our upcoming variant tracker, which, will assess new findings about each variant of the SARS-CoV-2 virus, in a similar way to our vaccine tracker.

References
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