Why the Omicron Variant Might Still Be Around

Where’s the pi?

Last year, the WHO (World Health Organization) began assigning Greek letters to new variants of the coronavirus that cause concern. The organization started with alpha and quickly moved through the Greek alphabet over the next few months. When the omnitron arrived in November, it was the 13th variant baptized in less than a year.

However, ten months have passed since the omicron’s debut, and the next letter in line, pi, still hasn’t arrived.

This does not mean that Sars-CoV-2, the coronavirus that causes Covid-19, has stopped evolving. But it may have entered a new stage. In the past year, more than a dozen common viruses have independently mutated into major public health threats. However, now all the most significant variations of the virus are descended from a single lineage: omicron.

“Based on what is currently being detected, it looks like the future of Sars-CoV-2 will evolve from the omicron,” said David Robertson, a virus specialist at the University of Glasgow in Scotland.

It also appears that the omicron has a remarkable ability to keep evolving. One of the newer subvariants, called BA.2.75.2, can evade immune reactions better than all previous forms of omicron.

For now, BA.2.75.2 is extremely rare, accounting for just 0.05% of the coronaviruses that have been sequenced worldwide in the last three months. But this was once true for other omicron subvariants that later came to dominate the world. If BA.2.75.2 becomes widespread this winter, it could diminish the effectiveness of Moderna’s and Pfizer’s newly authorized booster vaccines.

Every time Sars-CoV-2 replicates inside a cell, it can mutate. On rare occasions, the mutation can help Sars-CoV-2 replicate more quickly. Or it could help the virus stave off antibodies from previous Covid-19 flare-ups.

This beneficial mutation may become more common in a single country before disappearing. Or you can rule the world.

In principle, Sars-CoV-2 followed the slow and steady course that scientists had expected based on other coronaviruses. Its evolutionary tree gradually split into branches, each gaining a few mutations. Evolutionary biologists accompanied them with useful but obscure codes. Nobody paid much attention to the codes anymore, because they made little difference to the degree of illness caused by the virus in people.

But then a strain, initially known as B.1.1.7, defied expectations. When British scientists discovered it in December 2020, they were surprised to see that it contained a unique sequence of 23 mutations. These mutations allowed it to spread much faster than other versions of the virus.

Within a few months, several other worrisome variants had surfaced across the world – each with its own combination of mutations, each with the potential to spread rapidly and cause a wave of death. To facilitate communication about them, the WHO created its Greek system. B.1.1.7 has become alpha.

Different variants have experienced different levels of success. Alpha went on to dominate the world, while beta only grew in South Africa and a few other countries before losing steam.

What made the variants even more intriguing was that they arose independently. Beta is not descended from alpha. Instead, it came up with its own set of new mutations from a different branch of the Sars-CoV-2 tree. The same goes for all variants of the Greek name, up to the omicron.

It is likely that most of these variants got their mutations by hiding. Instead of jumping from host to host, they created chronic infections in people with weakened immune systems.

Unable to mount a strong attack, these victims harbored the virus for months, allowing it to accumulate mutations. When it finally emerged from its host, the virus had a surprising array of new capabilities — finding new ways to invade cells, weaken the immune system and evade antibodies.

“When it comes out, it’s like an invasive species,” said Ben Murrell, a computational biologist at the Karolinska Institute in Stockholm (Sweden).

The omicron did particularly well in this genetic lottery, gaining more than 50 new mutations that helped it find new pathways in cells and infect people who had been vaccinated or infected previously. As it spread across the world and caused an unprecedented increase in cases, it drove most other variants to extinction.

“The genetic innovations seen in the omicron were much more profound, as if it was a new species and not just a new strain,” said Darren Martin, a virus specialist at the University of Cape Town (South Africa).

But it soon became clear that the name “omicron” concealed a complex reality. After the original omicron virus evolved in the fall of 2021, its descendants split into at least five branches, known as BA.1 to BA.5.

Over the next few months, the subvariants took turns rising to dominance. BA.1 was the first, but was soon superseded by BA.2. Each was distinct enough from the others to escape some of the immunity of its predecessors. This summer, BA.5 was on the rise.

The US Food and Drug Administration responded by inviting vaccine manufacturers to produce booster doses that included a protein from BA.5 along with one from the original version of the virus. These boosters are now being released to the public at a time when BA.5 is causing 85% of all Covid-19 cases in the United States.

BA.5, however, could disappear in the rearview mirror in winter, the scientists said. The omicron continued to evolve — probably at times hopping between hosts and sometimes hiding for months in one.