COVID-19: The Omicron Variant

Sarah Bunn

Viruses constantly change and mutate when they reproduce themselves. Some of these mutations disappear, but any mutation that provides a benefit to the virus can become dominant in the population. Viruses with new mutations are called variants.
Some variants of the SARS-CoV-2 virus, which causes COVID-19, are of concern as they may have the potential to spread more easily between people. They may also make vaccines less effective.
The Omicron variant has multiple mutations to its spike protein, which is found on the virus’s surface. The spike protein plays a role in infecting cells. There are concerns that the mutations could make it harder for people’s immune systems to fight off the variant.
There is an extremely high level of uncertainty about the significance of the Omicron variant on the course of the pandemic. While Omicron has the potential to cause a new wave of infections, scientists do not yet know what its impact will be.
If Omicron is found to be a problem, it may take several months before a new vaccine can be developed, and some of the of the treatments for COVID-19 may be less effective. Anti-viral drugs may have to play a more important role in treating those with COVID-19.
PCR tests can detect those infected with the Omicron variant. It is likely that lateral flow tests will detect infections caused by Omicron; research is underway to verify this.
It will take at least two to three weeks to collect and analyse data that could start to resolve some of these uncertainties.

Understanding viral mutations and why they matter

The SARS-CoV-2 virus that causes COVID-19 contains a single strand of genetic material called RNA, surrounded by a membrane covered with proteins. The strand of RNA is the genome, which contains around 30,000 letters of genetic code that carry instructions for making proteins, including the spike protein that is found on the viral surface. The spike protein is the part of the virus that attaches to human cells so that the virus can infect them. This protein is recognised by the body’s immune system as foreign; this stimulates an immune response including the production of antibodies that can neutralise the virus. Immunisation with a COVID-19 vaccine or having had a previous infection means that people will already have antibodies to the spike protein.

The process by which viruses replicate is prone to errors, which introduces changes to the genetic sequence called mutations. These mutations mean that there are multiple forms of the virus called variants. Some mutations can be detrimental to the virus and will not persist, while others might confer properties that allow new variants to out-compete others that are circulating. Variants with advantageous mutations that allow them to continue replicating are described as “fit”. The fittest variant so far is the Delta variant.

Global surveillance of new variants

Scientists track the evolution of viral variants by analysing the genetic code from samples of the virus circulating in the population. New viral variants emerge regularly and are detected and monitored by international and national public health organisations. The international research community uses databases like GISAID to share genetic data openly and quickly, allowing for rapid analysis of the impacts on public health. Viruses with new mutations can be declared as a variant of concern. This means that experts think that there is a risk that the variant has the potential for causing more severe disease, more deaths, increased transmissibility, resistance to treatments, or evading immunity conferred by vaccination or previous infection. The dominant variant that has been responsible for almost all COVID-19 infections in the UK since winter 2020 is the Delta (B.1.617.2) variant. The questions and uncertainties about Omicron are similar to those that arose when other new variants emerged.

What is the Omicron variant?

A new variant was reported to the World Health Organization (WHO) on 24 November by researchers in South Africa. It is designated as variant B.1.1.529 and named Omicron. It was declared as a Variant of Concern by the WHO 2 days later. The first specimens containing the variant were collected in South Africa (8 November) and Botswana (11 November). The genome of the variant was sequenced and shared internationally on 22 November. It is not certain that the variant first emerged in South Africa.

Scientists are concerned that the changes seen in the biology of the variant could mean that the virus is more transmissible or could be more likely to infect people even if they have been vaccinated or had a previous infection.

The biology of the Omicron variant

Analysis of the Omicron variant’s genetic code shows that it contains an unusually high number of mutations compared with other variants (see image below). Some of these individual mutations had already been seen in other SARS-CoV-2 variants, while some are new. However, Omicron has accumulated multiple mutations (~50), many of which (26–32) are located on the spike protein. The number and location of the mutations is a concern since they relate to areas of the spike protein that are involved in virus transmissibility and recognition of the virus by antibodies. Other changes concern other parts of the virus, including a special protein called a nucleoprotein that is linked with the virus’s “fitness” in human cells. Fitness is a term used to describe how well the virus can infect hosts and replicate.

Omicron variant spike protein mutations

Spike protein structures of the SARS-CoV-2 virus showing mutations of the Omicron variant. — Spike protein structures of the SARS-CoV-2 virus showing mutations of the Omicron variant

Image credit: MRC-University of Glasgow Centre for Virus Research.

Why are scientists concerned about the Omicron variant?

After a COVID-19 infection or vaccination, a mixture of antibodies to the virus is made, which react to different parts of the spike protein. Therefore, if the virus has a mutation on one part of the spike protein which means that some antibodies cannot neutralise the virus, others can act on a different part of the protein. This creates redundancy in the immune response, giving people extra protection. Since Omicron has mutations at all the main sites that antibodies recognise, scientists are concerned that the variant has the potential to evade the immune response mediated by antibodies. This can be tested in laboratory studies and this research is already underway. However, the immune system and response is complex, with protection also mediated by other specialised immune cells. Scientists think that this part of the immune response is less susceptible to viral mutations than the antibody response.

Key uncertainties and research questions about Omicron

There is very high degree of uncertainty as to how Omicron’s characteristics will influence the course of the pandemic, how it will affect people and the measures that might be needed to protect public health. The World Health Organization published an Omicron technical briefing on 28 November. The New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) advises the UK Government on respiratory viruses. It has published its opinion on the possible impacts of Omicron, based on available data up to 25 November. There are five main questions, with information here drawn from WHO and NERVTAG analysis and other relevant sources.

How transmissible is Omicron?

It is highly likely that there is extensive transmission of Omicron.
It is not yet clear if Omicron is more transmissible than other variants, including the Delta variant.
Omicron has the potential to cause a new wave of infections in the UK; the magnitude of any wave is uncertain.

The first cases of infection with Omicron were detected in South Africa and Botswana. (There are no clear data yet to suggest that this is where the variant originated). Cases involving Omicron have increased rapidly in South Africa. South Africa’s National Institute for Communicable Diseases routinely analyses samples to monitor the genomes of circulating variants. Analysis of sampled genomes shows that Omicron has overtaken Delta, particularly in some regions of South Africa. While Delta was found in 79% of samples analysed in October, Omicron was found in 74% of samples in November. Experts are not certain if this rise in cases is due to increased transmissibility of Omicron or if other factors could account for it. For example, bias in sampling for genome testing may mean that the figures do not represent the true proportion of the variants circulating in the population. Other possible contributory factors concern local epidemiological circumstances; COVID-19 vaccine coverage is relatively low in South Africa (43% of all adults are fully vaccinated).

The variant has quickly spread across the world. A WHO briefing on 1 December reports that 23 countries have reported cases. Cases have been reported in people without connections to travel to South Africa, indicating that community transmission is established in numerous locations. The UK Health Security Agency is monitoring the spread of the variant. As of 2 December, there were 42 reported cases in the UK in 6 regions in England and Scotland. Although the UK Government has introduced temporary targeted measures to prevent the spread of Omicron (self-isolation for the infected person and their contacts regardless of their vaccination status; PCR testing for international arrivals; mandatory face coverings in some settings) it is inevitable that Omicron will spread.

Analysis of the spread of Omicron and a better understanding of the role of the variant’s mutations are needed to understand the variant’s transmissibility. Real-time analysis on the variant’s spread will emerge daily.

Does Omicron cause more severe disease or lead to more deaths?

There are not enough data to determine if Omicron causes more severe disease or deaths.

It will take a few weeks to determine if infections caused by Omicron cause more severe illness or increase the risk of someone dying. This is because there are no reliable laboratory techniques that can measure immunity to serious disease or predict outcomes; data have to come from real cases. There is also a lag between people becoming infected and developing an infection that could lead to hospitalisation. Real-time data are collected to see how many people are infected, who is hospitalised and whether they recover. Since the emergence of the variant coincided with a steep rise in COVID-19 infections in South Africa, it is likely that the first clinical data that can answer this question will come from there.

Can Omicron be detected by PCR and Lateral Flow Tests?

PCR tests can detect Omicron infections. Experts are confident that lateral flow tests can detect Omicron infections, but this needs to be verified.

PCR and lateral flow tests are molecular tests to detect active infections. PCR tests are processed in laboratories with results in 24-48 hours, whereas lateral flow tests (also called antigen tests) are used by individuals who process the sample themselves and receive a result in 20 minutes.

The World Health Organization states that PCR tests can detect Omicron infections. Most PCR tests target several parts of the viral genome; one target is the S-gene (that encodes the spike protein). As Omicron has a mutation here, that means that this part of the PCR test will fail. This is called S-gene drop-out or target failure. While not 100% accurate, it can be used as a proxy method for tracking the variant, especially if other dominant circulating variants are S-gene positive, as the Delta variant is. Other parts of the Omicron genome will be detected by PCR tests, so labs can still identify positive cases.

The UK has large laboratories (Lighthouse Laboratories) that can rapidly test large volumes of samples, with other testing capacity provide by smaller facilities. It is reported that 35-̶ 50% of the laboratories that run large-scale community case testing use the test can detect S-gene target failure.

A lateral flow test cannot tell someone which variant they are infected with. Scientists in South Africa have expressed a view that lateral flow tests will still tell someone if they are infected, including with the Omicron variant. This view has been reinforced recently through a rapid assessment by FIND (a global alliance focused on diagnostic technology), although this is still being verified.

Will existing COVID-19 vaccines work against Omicron?

Omicron has the potential to partly escape the immunity conferred by vaccination or a previous infection.
The extent to which current vaccines can protect against Omicron infection is unknown.
It is possible that vaccine effectiveness against severe disease could be reduced.
Developing new vaccines that can protect against new variants is an important countermeasure but will take several months.

There is a high degree of uncertainty as to how well existing vaccines will protect people from infections caused by the Omicron variant. Overall, scientists are cautiously optimistic that existing vaccines will be effective to some extent, but the degree of protection is uncertain.

A study by scientists in South Africa (which has not yet been peer reviewed) has analysed how many people who had previously had a COVID-19 infection were re-infected during waves of infection cause by the Beta, Delta and Omicron variants. This is a very large dataset using national health data of all confirmed cases, involving records from 35,670 people who have had at least 2 infections. Their data shows that the risk of reinfection with the Omicron variant is more than twice as likely compared with the other variants. The conclusion is that Omicron has the potential to evade immunity induced by a previous infection. The study does not answer if Omicron can similarly escape vaccine-induced immunity, but this is a real possibility.

Research is underway to measure how well antibodies that are made in response to COVID vaccination can neutralise the virus. This data could be available in under 2 weeks.

The Joint Committee on Vaccination and Immunisation (JCVI) advises the UK Government on immunisation programmes. In a statement on 29 November, it outlined that the best approach is to enhance each individual’s protection by offering an enhanced and expedited COVID-19 vaccine booster programme. This is based on the assumption that higher levels of antibodies induced by vaccines that were designed based on an earlier SARS-CoV-2 variant will protect against infections of the Omicron variant. The expanded booster programme will also minimise the impact of the Delta variant.

Advances in vaccine technologies mean that manufacturers can adapt COVID-19 vaccines quickly. For vaccines based on genetic technologies, like the Pfizer/BioNTech vaccine and the Spikevax (previously known as Moderna), this can be done in about 3 months.

Will COVID-19 treatments work against Omicron?

It is likely that existing monoclonal antibody treatments may be ineffective in people infected with the Omicron variant. If so, these treatments will need modification.
The role for anti-viral drugs in the pandemic response may become more important.

There are a range of drugs used to treat infections. These include anti-inflammatories, anti-viral drugs and therapies called monoclonal antibodies.

Anti-inflammatories and some drugs that target specific aspects of the immune system will remain effective.

Monoclonal antibody therapies are designed to act on the spike protein and are recommended for use in some hospitalised patients. The effectiveness of these types of treatment can be assessed in laboratory tests which measure the extent to which the antibodies are able to neutralise the Omicron variant. Pharmaceutical companies routinely evaluate their products’ effectiveness as new variants emerge, and can redesign their therapies if necessary.

Anti-viral drugs approved for use in the UK include remdesivir (used to treat some hospitalised patients) and molnupiravir (a tablet used to treat mild to moderate disease in people who are at risk for developing more severe illness). The Government has purchased 480,000 courses of molnupiravir treatment. It has also bought 250,000 courses of an as yet unapproved Pfizer anti-viral called ritonavir. Since anti-viral drugs are likely to work as well against Omicron as against previous variants, they could have a more important role in the management of the pandemic.