Why are there so many new Omicron subvariants?

Biology experts Sebastian Duchene and Ash Porter on whether the virus is mutating faster and the implications for the future of Covid

By now, many of us are familiar with the Omicron variant of Sars-CoV-2, the virus that causes Covid. This strain of concern has changed the course of the pandemic, leading to a dramatic spike in cases around the world.

We’re also hearing more and more about new Omicron subvariants with names like BA.2, BA.4, and now BA.5. The concern is that these subvariants can lead to people becoming reinfected, leading to a further increase in cases.

Why are we seeing more of these new sub-variants? Does the virus mutate faster? And what is the impact on the future of Covid?

Why are there so many types of Omicron?

All viruses, including Sars-CoV-2, are constantly mutating. The vast majority of mutations have little to no effect on the virus’ ability to be transmitted from one person to another or cause serious illness.

When a virus accumulates a significant number of mutations, it is considered a different lineage (like another branch in a family tree). But a virus line is not called a variant until it has accumulated several unique mutations that are known to enhance the virus’s ability to transmit and/or cause more serious disease.

Such was the case for the BA line (sometimes known as B.1.1.529), referred to as the Omicron by the World Health Organization. Omicron has spread rapidly and represents almost all current cases with genomes sequenced worldwide.

As Omicron has spread rapidly and had many opportunities to mutate, it has also acquired specific mutations of its own. These have given rise to several sub-lines or sub-variants.

The first two were designated BA.1 and BA.2. The current list now also includes BA.1.1, BA.3, BA.4 and BA.5.

We have seen subvariants of previous versions of the virus, such as B. Delta. However, Omicron may have surpassed these due to its increased portability. As a result, subvariants of earlier viral variants are much rarer today and less value placed on tracking them.

Why are subvariants a big deal?

There is evidence that these omicron subvariants – particularly BA.4 and BA.5 – are particularly effective at reinfecting people with previous infections by BA.1 or other lineages. There is also concern that these subvariants could infect people who have been vaccinated.

We therefore expect a rapid increase in Covid cases over the coming weeks and months due to reinfections that we are already seeing in South Africa.

However, recent research suggests that a third dose of the Covid vaccine is the most effective way to slow the spread of Omicron (including subvariants) and prevent Covid-related hospitalizations.

Recently, BA.2.12.1 has also attracted attention because it has spread rapidly in the United States and was recently detected in wastewater in Australia. Alarmingly, even if someone has been infected with the Omicron subvariant BA.1, re-infection with sublineages BA.2, BA.4, and BA.5 is still possible due to their ability to evade immune responses.

Does the virus mutate faster?

One might think that Sars-CoV-2 is a super-fast leader when it comes to mutations. But the virus actually mutates relatively slowly. Influenza viruses, for example, mutate at least four times faster.

However, Sars-CoV-2 has “mutation sprints” for short periods, our research shows. During one of these sprints, the virus can mutate four times faster than normal for a few weeks.

After such sprints, the line will exhibit more mutations, some of which may provide an advantage over other lines. Examples include mutations that can help the virus become more easily transmitted, cause more severe disease, or evade our immune response, creating new variants.

Why the virus undergoes mutation sprints that lead to the emergence of variants is unclear. But there are two main theories about Omicron’s origins and how it accumulated so many mutations.

First, the virus may have evolved into chronic (persistent) infections in people who are immunocompromised (have a weakened immune system).

Second, the virus may have “jumped” to another species before infecting humans again.

What other tricks does the virus have?

Mutations are not the only way variants can arise. The Omicron XE variant appears to have arisen from a recombination event. Here, a single patient was simultaneously infected with BA.1 and BA.2. This coinfection resulted in a “genome swap” and a hybrid variant.

Other cases of Sars-CoV-2 recombination have been reported between Delta and Omicron, resulting in what has been dubbed Deltacron.

So far, recombinants do not appear to have higher transmissibility or cause more severe consequences. But that could change quickly with new recombinants. Scientists are therefore watching them closely.

What could we see in the future?

As long as the virus circulates, we will continue to see new virus lines and variants. Since omicron is currently the most common variant, we will likely see more subvariants of omicron and possibly even recombinant lineages.

Scientists will continue to track new mutations and recombination events (particularly with subvariants). They will also use genomic technologies to predict how these will occur and what impact they might have on the virus’ behavior.

This knowledge will help us limit the proliferation and influence of variants and subvariants. It will also guide the development of vaccines effective against multiple or specific variants.

Sebastian Duchene, ARC DECRA Fellow, The University of Melbourne, and Ash Porter, Research Officer, The Peter Doherty Institute for Infection and Immunity

This article was republished by The Conversation under a Creative Commons license. Read the original article.