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 swiftly worked its way 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 letter in line, pi, has yet to arrive.
That does not mean SARS-CoV-2, the coronavirus that causes COVID-19, has stopped evolving. But it may have entered a new stage. Last year, more than a dozen ordinary viruses independently transformed into major new public health threats. But now, all of the virus’s most significant variations are descending from a single lineage: Omicron.
“Based on what’s being detected at the moment, it’s looking like future SARS-CoV-2 will evolve from Omicron,” said David Robertson, a virus specialist at the University of Glasgow.
It’s also looking like Omicron has a remarkable capacity for more evolution. One of the newest subvariants, called BA.2.75.2, can evade immune responses better than all earlier forms of omicron.
For now, BA.2.75.2 is extremely rare, making up just 0.05 percent of the coronaviruses that have been sequenced worldwide in the past three months. But that was once true of other Omicron subvariants that later came to dominate the world. If BA.2.75.2 becomes widespread this winter, it may blunt the effectiveness of the newly authorized boosters from Moderna and Pfizer.
Every time SARS-CoV-2 replicates inside of a cell, it might mutate. On rare occasions, a mutation might help SARS-CoV-2 replicate faster. Or it might help the virus evade antibodies from previous bouts of COVID-19.
Such a beneficial mutation might become more common in a single country before fading away. Or it might take over the world.
At first, 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 kept track of them with codes that were useful but obscure. No one else paid much attention to the codes, because they made little difference to how sick the viruses made people.
But then one lineage, initially known as B.1.1.7, defied expectations. When British scientists discovered it, in December 2020, they were surprised to find it bore a unique sequence of 23 mutations. Those mutations allowed it to spread much faster than other versions of the virus.
Within a few months, several other worrying variants came to light around the world — each with its own combination of mutations, each with the potential to spread quickly and cause a surge of deaths. To make it easier to communicate about them, the WHO came up with its Greek system. B.1.1.7 became alpha.
Different variants experienced varying levels of success. Alpha came to dominate the world, whereas Beta took over only in South Africa and a few other countries before petering out.
What made the variants even more puzzling was that they arose independently. Beta did not descend from Alpha. Instead, it arose with its own set of new mutations from a different branch of the SARS-CoV-2 tree. The same held true for all the Greek-named variants, up to Omicron.
It’s likely that most of these variants got their mutations by going into hiding. Instead of jumping from one host to another, 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 eventually 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 gets 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, gaining more than 50 new mutations that helped it find new routes into cells and to 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 to extinction.
“The genetic innovations seen in Omicron were far more profound, as if it was a new species rather than just a new strain,” said Darren Martin, a virus specialist at the University of Cape Town.
But it soon became clear that the name “Omicron” hid 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 through BA.5.
Over the next few months, the subvariants took turns rising to dominance. BA.1 went first, but it was soon outcompeted by BA.2. Each one was distinct enough from the others to evade some of the immunity of its predecessors. By this summer, BA.5 was on the rise.
The US Food and Drug Administration responded by inviting vaccine-makers to produce booster shots that included a BA.5 protein along with one 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 percent of all COVID-19 cases in the United States.
But BA.5 could be fading in the rearview mirror by winter, scientists said. Omicron has continued to evolve — likely by sometimes jumping among hosts, and sometimes hiding for months in one of them.