Is Omicron more contagious than Delta? A virus evolution expert explains what researchers know and don't know

The omicron variant of the corona virus contains many mutations in the spike protein, which facilitate the penetration of the virus into cells

By: Suresh Kuchipudi, Professor of Infectious Diseases and Epidemiology, Penn State

A new variant of the corona virus named Omicron (B.1.1.529) was reported by researchers in South Africa on November 24, 2021, and was declared a "variant of concern" by the World Health Organization two days later. Omicron is unusual in that it is by far the most heavily mutated version to date of SARS-CoV-2, the virus that causes COVID-19.

The omicron variant has 50 mutations in total, 32 of which are on the spike protein alone. The spike protein - which creates a kind of protruding "handles" on the outside of the SARS-CoV-2 virus - helps the virus stick to cells so that it can enter them and reproduce. It is also the protein that most vaccines available today use to make the body produce antibodies that will neutralize the virus if it enters the body. By comparison, the delta variant has nine mutations. The greater number of mutations of the omicron variant may mean that it can be more infectious and/or be better at evading the immune system – the most worrisome feature.

I am a virologist who studies epidemics in the making in animals, to know how viruses emerge and an epidemic develops. My research group has been looking at various aspects of the COVID-19 virus, including its spillover into animals.

Why new versions of COVID-2 continue to appear?

While the unusually high number of mutations in the omicron variant is surprising, the emergence of another SARS-CoV-2 variant is not unexpected.

Through natural selection, random mutations accumulate in every virus. This process is accelerated in RNA viruses, including SARS-CoV-2. If and when a group of mutations gives a variant a survival advantage over its predecessors, it will compete with all other existing variants of the virus.

Does the greater number of mutations of the omicron variant mean that it is more dangerous and transmissible than delta? We just don't know yet. The conditions that led to the emergence of the variation are still unclear, but what is clear is that the number and shape of the mutations in the omicron are unusual.

One possible explanation for how viral variants with multiple mutations are created is through prolonged infection in a patient whose immune system is suppressed - a situation that can lead to rapid viral evolution. Researchers speculated that some of the early variants of SARS-CoV-2, such as the alpha variant, may have been created this way. However, the unusual structure and many mutations of the omicron variant make it very different from all other SARS-CoV-2 strains, raising questions about how it originated.

Another possible source of variants could be animals infected with the virus from humans. The virus that causes COVID-19 can infect several animal species, including mink, tigers, lions, cats and dogs. In yet-to-be-peer-reviewed research, an international team I lead recently reported widespread coronavirus infection in captive white-tailed deer in the US. Therefore, we also cannot rule out the possibility that the omicron variant appeared in a host animal and underwent rapid evolution.

How the delta version became dominant worldwide

The delta variant is 40% to 60% more infectious than the alpha variant and almost twice as much as the original SARS-CoV-2 virus first identified in China. The increased transmissibility of the delta variant is the main reason researchers believe it was able to compete with other variants to become the dominant strain.

A key factor in viral fitness is the replication rate of the virus - or how quickly a virus can make more copies of itself. The delta variant replicates faster than earlier versions of SARS-CoV-2, and a yet-to-be-peer-reviewed study estimated that it produces 1,000 times more virus particles than its predecessors.

In addition, people infected with the delta variant produce and spread more virus, which is another potential mechanism for its increased ability to spread. Studies indicate that a possible explanation for the increased ability of the delta variant to replicate is that mutations in the spike protein led to a more efficient binding of the spike protein to its host, via the ACE-2 receptor.

The delta variant also acquired mutations that allowed it to evade neutralizing antibodies that play a critical role in the body's defense against an invading virus. This could explain why, as many reports have shown, the vaccines against COVID-19 were slightly less effective against the delta variant. This combination of high transmissibility and immune evasion may help explain how the delta variant became so successful.

Research also shows that people infected with the delta variant have a higher risk of hospitalization compared to those infected with the original SARS-CoV-2 and earlier variants. One particular mutation in the spike protein of the delta variant - the P681R mutation - is thought to be a key contributor to improving its ability to enter cells and cause more severe disease.

Will omicron replace Delta?

It is too early to say whether the omicron variant is more suitable than delta or whether it will become dominant. Omicron shares some mutations with the delta variant but has other quite different mutations as well. But one of the reasons we in the research community are particularly concerned is that the omicron variant has ten mutations in the receptor linker – the part of the spike protein that interacts with the ACE-2 receptor and mediates entry into cells – compared to only two in the delta version.

Suppose that the combination of all the mutations in omicron makes it more or better transmitted by immune evasion than delta. In that case, we could see the spread of this version around the world. However, it is also possible that the unusually high number of mutations could harm the virus and make it unstable.

It is very likely that Omicron is not the end of the game and that more SARS-CoV-2 variants will appear. As SARS-CoV-2 continues to spread among humans, natural selection and adaptation will result in the formation of more potentially more infectious variants than delta.

We know from influenza viruses that the viral adaptation process never ends. Lower vaccination rates in many countries mean that there are still many susceptible hosts to the virus, and that it will continue to circulate and mutate as long as it can spread. The appearance of the omicron variant is another reminder of the urgency to vaccinate to stop the further spread and development of SARS-CoV-2.

For an article in The Conversation

More of the topic in Hayadan:

• The omicron species - what do we know?
• What is the spike protein of the corona and why is it feared that the mutation will be resistant to vaccines
• Everything you wanted to know about the delta breed, but didn't feel comfortable asking
• Researchers from South Africa explain how the new Omicron version was found and what we know so far