Where is pi?
Last year, the World Health Organization began assigning Greek letters to worrying new variants of the coronavirus. The organization started with alpha and quickly went through the Greek alphabet in the months that followed. When omicron arrived in November, it was the 13th named variant in less than a year.
But 10 months have passed since omicron’s debut, and the next online letter, pi, has yet to arrive.
This does not mean that SARS-CoV-2, the coronavirus that causes COVID-19, has stopped evolving. But he may have entered a new stage. Last year, more than a dozen ordinary viruses independently morphed into major new threats to public health. But now, all the most important variations of the virus descend from a single lineage: omicron.
“Based on what’s being detected right now, it looks like the future SARS-CoV-2 will evolve from omicron,” said David Robertson, a virus expert at the University of Glasgow.
It also seems that omicron has a remarkable ability for more evolution. One of the newer sub-variants, called BA.2.75.2, can evade immune responses better than all earlier omicron forms.
For now, BA.2.75.2 is extremely rare, representing only 0.05% of the coronaviruses that have been sequenced worldwide in the past three months. But that was once the case with other omicron sub-variants that later dominated the world. If BA.2.75.2 becomes widespread this winter, it could blunt the effectiveness of newly authorized boosters from Moderna and Pfizer.
Each time SARS-CoV-2 replicates inside a cell, it can mutate. On rare occasions, a mutation could help SARS-CoV-2 replicate faster. Or it could help the virus evade antibodies from previous episodes of COVID-19.
Such a beneficial mutation could become more common in a single country before disappearing. Or he could take over the world.
At first, SARS-CoV-2 took the slow, steady course that scientists expected based on other coronaviruses. Its evolutionary tree gradually split into branches, each gaining a few mutations. Evolutionary biologists followed them with useful but obscure codes. Nobody else paid much attention to the codes because they had little bearing on how viruses made people sick.
But one lineage, originally known as B.1.1.7, defied expectations. When British scientists discovered it, in December 2020, they were surprised to find that it carried a unique sequence of 23 mutations. These mutations allowed it to spread much faster than other versions of the virus.
Within months, several other disturbing variants have emerged around the world – each with its own combination of mutations, each with the potential to spread rapidly and cause a wave of deaths. To facilitate communication about them, the WHO has devised its Greek system. B.1.1.7 became alpha.
Different variations have had varying levels of success. The alpha came to dominate the world, while the beta only took over in South Africa and a few other countries before running out.
What made the variants even more confusing was that they appeared independently. The beta did not come from the alpha. Instead, it emerged with its own set of new mutations from a different branch of the SARS-CoV-2 tree. The same goes for all Greek name variants, up to omicron.
It is likely that most of these variants obtained their mutations while hiding. Instead of jumping from one host to another, they created 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. When it finally emerged from its host, the virus had a startling range of new abilities – 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.
Omicron did particularly well in this genetic lottery, winning more than 50 new mutations that helped it find new pathways in cells and infect people who had been vaccinated or previously infected. As it spread around the world and caused an unprecedented spike in cases, it drove most other variants into extinction.
“The genetic innovations seen in the omicron were much deeper, as if it were a new species rather than just a new strain,” said Darren Martin, a virus expert at the University of Cap.
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, called BA.1 to BA.5.
Over the following months, the sub-variants took turns becoming dominant. BA.1 went first, but was quickly overtaken 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 asking vaccine makers to produce booster shots that include a BA.5 protein as well as a protein from the original version of the virus. These boosters are now being rolled out to the public, at a time when BA.5 is responsible for 85% of all COVID-19 cases in the United States.
But BA.5 could disappear in the rearview mirror by winter, scientists have said. Omicron continued to evolve – probably sometimes jumping among hosts and sometimes hiding in one for months.
Since these new lineages belong to omicron, they do not have their own Greek letter. But that doesn’t mean they’re just a slight twist on the original. Antibodies that might cling to earlier forms of omicron perform poorly against newer ones.
“They probably would have been given different Greek letters,” Robertson said.
BA.2.75.2 is among omicron’s most recent grandchildren, identified last month. It’s also the most evasive omicron to date, according to Murrell. In lab experiments, he and his colleagues tested BA.2.75.2 against 13 monoclonal antibodies that are either in clinical use or in development. He escaped all but one, bebtelovimab, made by Eli Lilly.
They also tested antibodies from recent blood donors in Sweden. BA.2.75.2 performed considerably better at evading these defenses than the other omicron sub-variants.
The researchers published their study online on September 16. Peking University researchers came to similar conclusions in a study published the same day. Both have yet to be published in a scientific journal.
Murrell cautioned that scientists have yet to conduct experiments that will show the effectiveness of BA.5 versus BA.2.75.2 booster shots. He suspected that obtaining a large amount of BA.5 antibodies would provide some protection, especially against serious diseases.
“It’s still important, but we’ll have to wait for the data to come out to see exactly how big the boosting effect is,” Murrell said.
There is no reason to expect BA.2.75.2 to be the end of the evolutionary line. As immunity grows stronger from previous versions of omicron, newer versions will be able to evolve to evade it.
“I don’t think it’s going to hit a wall in the mutational space,” said Daniel Sheward, postdoctoral researcher at the Karolinska Institutet and co-author of the new study.
Lorenzo Subissi, an infectious disease expert at the WHO, said the organization does not give lineages like BA.2.75.2 Greek letters because they closely resemble the original omicron viruses. For example, it appears that all omicron lines use a particular pathway to enter cells. As a result, it is less likely to cause serious infections, but perhaps better able to spread than previous variants.
“WHO only names a variant when it is concerned that additional risks will be created that require new public health measures,” Subissi said. But he didn’t rule out a pi in our future.
“This virus still remains largely unpredictable,” he said.
This article originally appeared in The New York Times.