Why Omicron can stick around

Where is Pi?

Last year, the World Health Organization began assigning Greek letters to disturbing new variants of the coronavirus. The organization started with Alpha and quickly worked its way through the Greek alphabet in the months that followed. When the Omicron arrived in November, it was the 13th variant to be named in less than a year.

But 10 months have passed since Omicron launched, and the next letter in the line, Pi, has yet to arrive.

That doesn’t mean that SARS-CoV-2, the coronavirus that causes Covid-19, has stopped growing. But it may have entered a new phase. Last year, more than a dozen common viruses independently mutated into new public health threats. But for now, all the most important variants of the virus are in a single lineage: Omicron.

“Based on what is being detected at this time, it seems likely that future SARS-CoV-2 will evolve from Omicron,” said David Robertson, a virologist at the University of Glasgow.

It seems that Omicron has a significantly more evolved ability. One of the newest subvariables, called BA.2.75.2, can dodge immune responses better than all previous forms of Omicron.

Currently, BA.2.75.2 is extremely rare, representing only 0.05% of coronaviruses that have been sequenced worldwide in the past three months. But that was once true of other Omicron subspecies that would later rule the world. If BA.2.75.2 becomes popular this winter, it could reduce the effectiveness of newly commissioned boosters from Moderna and Pfizer.

Every time SARS-CoV-2 replicates inside a cell, it can mutate. In rare cases, a mutation can help SARS-CoV-2 replicate more quickly. Or it could help the virus evade antibodies from previous Covid episodes.

Such a beneficial mutation may become more common in a country before disappearing. Or it could take over the world.

At first, SARS-CoV-2 followed the slow and steady path that scientists expected based on other coronaviruses. Its evolutionary tree gradually splits into many branches, each of which gains several mutations. Evolutionary biologists have tracked them down with useful but little-known codes. No one else pays much attention to the codes, because they make no difference to the way viruses infect humans.

But then a lineage, originally called B.1.1.7, defied expectations. When British scientists discovered it, in December 2020, they were surprised to discover it carried a unique sequence of 23 mutations. Those mutations allow it to spread much faster than other versions of the virus.

Within a few months, a number of other disturbing variants came to light around the world – each with its own combination of mutations, each capable of spreading rapidly and causing serious illness. resulted in a series of deaths. To make it easier to exchange information about them, WHO introduced its Greek system. B.1.1.7 becomes Alpha.

Different variations experience varying degrees of success. Alpha took over the world, while Beta only took over in South Africa and a few other countries before disappearing.

What makes variations even more confusing is that they arise independently. Beta version does not drop from Alpha. Instead, it arose with a series of new mutations from another branch of the SARS-CoV-2 tree. The same is true for all variants with Greek names, down to Omicron.

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

Unable to mount a powerful attack, these victims harbored the virus for months, allowing it to accumulate mutations. Finally, when emerging from the host, the virus has an amazing new set of abilities – finding new ways to enter cells, weakening the immune system and evading antibodies.

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

Omicron has done well in this genetic lottery, picking up more than 50 new mutations that help it find new routes into cells and infect people who have been vaccinated or previously infected. As it spread around the world and caused an unprecedented spike in cases, it drove most other variants to extinction.

“The genomic discoveries in Omicron are much more profound, as if it were a new species and not just a new strain,” said Darren Martin, a virologist at the University of Cape Town.

But apparently the name “Omicron” conceals a complicated reality. After the original Omicron virus developed in the fall of 2022, its descendants split into at least five clades, known as BA.1 through BA.5.

Over the next few months, the secondary variables took turns to dominate. BA.1 went first, but it was soon dropped by BA.2. Each is different enough from the others to avoid some of the immunity of its predecessors. This summer, BA.5 has increased.

The US Food and Drug Administration responded by inviting vaccine manufacturers to produce booster shots that include a BA.5 protein along with a shot from the original version of the virus. Those boosters are now rolling out to the public, at a time when BA.5 is causing 85% of all Covid cases in the United States.

But BA.5 can fade in the rearview mirror in winter, scientists say. Omicrons have continued to evolve – possibly by sometimes hopping between hosts, and sometimes hiding for months in one of them.

Since these new lineages belonged to Omicron, they did not yet have a Greek letter of their own. But that doesn’t mean they’re just a bit of a variation on the original. Antibodies can bind to earlier forms of Omicrons less well than newer forms.

“They can be thought of as different Greek letters,” says Dr. Robertson.

BA.2.75.2 is one of the latest among Omicron’s grandchildren, identified last month. According to Dr. Murrell, it is also the most elusive Omicron species. In laboratory experiments, he and his colleagues tested BA.2.75.2 against 13 monoclonal antibodies in clinical use or under development. It evades all but one of them, bebtelovimab, performed by Eli Lilly.

They also tested for antibodies from recent blood donors in Sweden. BA.2.75.2 essentially did a significantly better job of getting rid of those defenses than the other Omicron subvariants did.

The researchers posted their study online on Friday. Researchers at Peking University came to the same conclusion in a study published the same day. Both have not been published in scientific journals.

Dr. Murrell cautioned that scientists have yet to perform experiments showing the effectiveness of BA.5 booster shots on BA.2.75.2. He suspects that delivering large amounts of the BA.5 antibody will provide some protection, especially against severe disease.

“It’s still important, but we’ll have to wait for the data to come out to see exactly what the magnitude of the boosting effect is,” Dr Murrell said.

There is no reason to expect that BA.2.75.2 will be the end of the evolutionary line. As immunity builds over previous versions of Omicron, new versions will be able to evolve to be able to avoid it.

“I didn’t think it would hit a wall in mutant space,” said Daniel Sheward, a postdoctoral researcher at the Karolinska Institutet and co-author of the new study.

Lorenzo Subissi, an infectious disease expert at the WHO, said that the organization did not give Greek letters to family lines like BA.2.75.2 because they resembled the original Omicron viruses. For example, it appears that all Omicron lineages use a particular pathway to enter cells. As a result, it is less likely to lead to severe infection but is more contagious than earlier variants.

Dr Subissi said: “WHO only named a variant when it was concerned that additional risks were being created that required new public health action. But he doesn’t rule out some of our future Pis.

“This virus remains largely unpredictable,” he said.