How Did It Emerge and Is It More Contagious Than Delta? A Virus Evolution Expert Explains

By Suresh V. Kuchipudi, Penn State University December 5, 2021

A new variant called omicron (B.1.1.529) was reported by researchers in South Africa on November 24, 2021, and designated a “variant of concern” two days later by the World Health Organization. Omicron is highly unusual because it is by far the most highly mutated variant to date of SARS-CoV-2, the virus that causes COVID-19.

The omicron variant has a total of 50 mutations, with 32 mutations on the spike protein alone. The spike protein — which forms protruding buds on the outside of the SARS-CoV-2 virus — helps the virus attach to cells so it can gain entry. It is also the protein that all three vaccines currently available in the US use to induce protective antibodies. In comparison, the delta variant has nine mutations. The higher number of mutations in the omicron variant may mean it is more transmissible and/or better at evading immune protection – a very worrying prospect.

I am a virologist who studies emerging and zoonotic viruses to better understand how new epidemic or pandemic viruses arise. My research group has studied various aspects of the COVID-19 virus, including its spread to animals.

The omicron variant possesses numerous mutations in the spike protein, the button-like projections (in red) that allow the virus to invade other cells.

Why do new SARS-CoV-2 variants keep popping up?

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

Random mutations accumulate in any virus through natural selection. This process is accelerated in RNA viruses, including SARS-CoV-2. If and when a series of mutations confer a survival advantage for a variant over its predecessors, the variant will outperform all other existing virus variants.

Does the greater number of mutations of the ommicron variant mean it is more dangerous and transmissible than delta? We simply don’t know yet. The circumstances that led to the emergence of the variant are not yet clear, but what is clear is that the sheer number and configuration of mutations in omicron is unusual.

One possible explanation for how viral variants with multiple mutations arise is through prolonged infection in a patient whose immune system is suppressed – a situation that can lead to rapid viral evolution. Researchers have hypothesized that some of the earlier SARS-CoV-2 variants, such as the alpha variant, may have come from a persistently infected patient. However, the unusual constellation and numerous mutations in the omicron variant make it very different from all other SARS-CoV-2 strains, raising questions about how it came about.

Another possible source of variants could be via animal hosts. The virus that causes COVID-19 can infect a variety of animal species, including minks, tigers, lions, cats and dogs. In a study not yet peer-reviewed, an international team I lead recently reported widespread infection by SARS-CoV-2 in free-living and captive white-tailed deer in the US. Therefore, we cannot exclude that the ommicron variant arose in an animal host through rapid evolution.

White-tailed deer have recently been identified as an important reservoir for SARS-CoV-2, the virus that causes COVID-19.

How the delta variant became globally dominant

Delta is between 40% and 60% more transmissible than the alpha variant and nearly twice as transmissible as the original SARS-CoV-2 virus first identified in China. The increased portability of the delta variant is the main reason researchers believe she was able to outperform other variants to become the dominant species.

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

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

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

Studies also show that people infected with the delta variant have a higher risk of hospitalization compared to those infected with the original SARS-CoV-2 and early variants. A specific mutation on the spike protein of the delta variant – the P681R mutation – is believed to be a major contributor to its enhanced ability to enter cells and cause more severe disease.

Will ommicron replace delta?

It is too early to say whether the omicron variant is fitter than delta or will become dominant. Omicron shares some mutations with the delta variant, but also possesses others that are quite different. But one of the reasons we’re particularly concerned in the research community is that the omicron variant has 10 mutations in the receptor-binding domain — the part of the spike protein that interacts with the ACE-2 receptor and mediates entry into cells. – compared to only two for the delta variant.

Suppose the combination of all the mutations in omicron makes it either more transmissible or better at immune evasion than delta. In that case, we could see the spread of this variant worldwide. However, it is also possible that the unusually high number of mutations is harmful to the virus and makes it unstable.

It is very likely that the omicron variant is not the endgame and that more SARS-CoV-2 variants will emerge. As SARS-CoV-2 continues to spread among humans, natural selection and adaptation will result in more variants that are likely more transmissible than delta.

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

Written by Suresh V. Kuchipudi, Professor of Emerging Infectious Diseases, Penn State University.

This article was first published in The Conversation.