Omicron mutations already existed in infected patients months before becoming dominant

By now, many of us will be familiar with the omicron variant of SARS-CoV-2, the virus that causes Covid. This variant of concern changed the course of the pandemic, leading to a dramatic increase in cases around the world.

We also hear more and more about new omicron sub-variants with names like BA.2, BA.4 and now BA.5. The concern is that these subvariants may cause people to be reinfected, leading to another spike in cases. Why are we seeing more of these new sub-variants? Is the virus mutating faster? And what are the implications for the future of covid?

All viruses, including SARS-CoV-2, constantly mutate. The vast majority of mutations have little or no effect on the ability of the virus to spread from person to person or cause serious illness.

When a virus accumulates a substantial number of mutations, it is considered a different lineage (sort of like a different branch on a family tree). But a viral lineage is not labeled as a variant until it has accumulated several unique mutations known to enhance the ability of the virus to transmit and/or cause more severe disease.

Omicron mutations already existed in infected patients months before becoming dominant

This was the case for the BA lineage (sometimes known as B.1.1.529) which the World Health Organization (WHO) named omicron. Omicron spread rapidly, accounting for almost all current cases with sequenced genomes globally. Since omicron expanded and had many opportunities to mutate, it also acquired specific mutations of its own. These gave rise to several sublineages or subvariants.

The first two were labeled BA.1 and BA.2. The current list now also includes BA.1.1, BA.3, BA.4 and BA.5. We have already seen sub-variants of previous versions of the virus, such as delta. However, omicron outperformed them, possibly due to its greater transmissibility. Therefore, subvariants of earlier viral variants are much less common today and there is less emphasis on tracking them.

There is evidence that these omicron subvariants, specifically BA.4 and BA.5, are particularly effective at reinfecting people with previous infections of BA.1 or other lineages. There is also concern that these subvariants could infect people who were vaccinated.

So we expect to see a rapid increase in covid cases in the coming weeks and months due to reinfections, which we are already seeing in South Africa. Nevertheless, 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 hospital admissions associated with the disease.

Viruses constantly mutate
Viruses constantly mutate

Recently, BA.2.12.1 also drew attention because it has been spreading rapidly in the United States and has been detected in sewage in Australia. Alarmingly, even if someone was infected with the BA.1 subvariant of omicron, reinfection with the BA.2, BA.4, and BA.5 sublineages is still possible, due to their ability to evade immune responses.

One would think that SARS-CoV-2 is a super-fast runner 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 does “mutational sprints” for short periods of time, our research shows. During one of these speed races, the virus can mutate four times faster than normal for a few weeks.

After those runs, the bloodline has more mutations, some of which may provide an advantage over other bloodlines. Examples include mutations that can help the virus become more transmissible, cause more severe disease or evade our immune response, and thus new variants emerge.

It is not clear why the virus undergoes these mutational races that lead to the appearance of variants. But there are two main theories about the origins of omicron and how it accumulated so many mutations. First, the virus could have evolved into chronic (long-term) infections in people who are immunosuppressed (have a weakened immune system). Second, the virus could have “jumped” to another species, before re-infecting humans.

Mutation is not the only way variants can arise. The omicron XE variant appears to have resulted from an event of recombination. This is where a single patient was infected with BA.1 and BA.2 at the same time. This coinfection led to a “genome swap”” and a hybrid variant.

Other cases of SARS-CoV-2 recombination between delta and omicron were reported, resulting in what was named deltacron. So far, the recombinants do not appear to have greater transmissibility or cause more serious effects. But this could change rapidly with new recombinants. So scientists are monitoring them closely.

Specialists began to study whether the vaccines will protect against the new subvariants
Specialists began to study whether the vaccines will protect against the new subvariants

As long as the virus is circulating, we will continue to see new lineages and variants of the virus. As omicron is the most common variant today, we are likely to see more sub-variants of omicron and potentially 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 might occur and any effect they might have on the behavior of the virus. This knowledge will help us limit the spread and impact of variants and subvariants. It will also guide the development of effective vaccines against multiple or specific variants.

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