In November 2021, almost two years after the coronavirus appeared in Wuhan and spread across the world, the surprises seemed to be over. More than four billion people have been vaccinated against the virus and five million have died. Two new variants, known as Alpha and Delta, rose and then ebbed. As Thanksgiving approached, many Americans were planning to resume travel for the holiday.
And then, the day after Turkey, the pandemic had another major surprise in store. Researchers in Botswana and South Africa alerted the world that a highly mutated version of the virus had emerged and was spreading rapidly. Omicron, as the World Health Organization called this variant, quickly overtook other forms of the virus. He remains dominant today, on his second birthday.
In the two years since its emergence, Omicron has proven itself not only incredibly contagious, but also an evolutionary marvel, challenging many assumptions virologists had before the pandemic. She gave birth to an impressive number of descendants, who became much more adept at evading immunity and finding new victims.
“It was almost like there was another pandemic,” said Adam Lauring, a virologist at the University of Michigan.
Dr. Lauring and other Omicron watchers are now trying to make sense of the past two years in order to prepare for the future. It is possible that Omicron will become a permanent part of life, mutating regularly like the seasonal flu. But researchers warn that the virus still has the capacity to surprise us, especially if we stop paying attention.
When Omicron was first discovered, the United States and other countries mistakenly believed they could stop its spread by banning travel from South Africa. In fact, it had already spread widely. Within days, Britain, Italy and Germany discovered Omicron in positive Covid tests.
Omicron’s gift for rapid propagation was the result of dozens of mutations. They modified the surface of the virus, so that antibodies produced by vaccines or previous infections cannot stick tightly to it and prevent the virus from invading cells.
“It was the first virus to significantly understand how to evade immunity,” said Dr. Jacob Lemieux, an infectious disease specialist at Massachusetts General Hospital.
Dr. Lemieux and many other Omicron experts suspect that the variant acquired its new mutations by infecting a single person with a weakened immune system. Immunocompromised people can only fight off some of the coronaviruses in their body during an infection, allowing those that remain to acquire mutations that can thwart the immune system.
“It becomes like a laboratory for virus evolution,” said Peter Markov, a virologist at the London School of Hygiene and Tropical Medicine.
As epidemiologists tracked the Omicron wave in late 2021, they noticed a crucial difference from previous waves. Compared to previous variants, Omicron has hospitalized a smaller fraction of infected people. One reason for this change was that many people were immune to earlier forms of the coronavirus. Our immune defenses include not only antibodies, but also special immune cells that can recognize and kill infected cells. This second line of defense held up even to Omicron, preventing many of the new infections from becoming serious.
Yet Omicron caused so many new infections — the first wave infected nearly half of all Americans, according to a recent estimate — that it still triggered a devastating wave of hospitalizations.
The Omicron wave hit the United States and most other countries in early 2022. China managed to contain the waves thanks to its “zero Covid” policy, but protests against its brutality are became so intense that President Xi Jinping abruptly abandoned it in November 2022. The floodgates opened: in a few weeks, more than a billion Chinese contracted Omicron, leading to more than a million deaths.
As Omicron moved from person to person, his descendants acquired more mutations. Sometimes two Omicron viruses ended up in the same cell, which produced new hybrid viruses with a mixture of their genes. One of these so-called recombinations hit the jackpot by mixing two sets of evasive mutations. The result was a new hybrid called XBB.
XBB easily infects people, even those who have previously been infected with Alpha, Delta, or earlier forms of Omicron. As a result, XBB became dominant in the United States in early 2023.
Vaccine makers have tried to keep up with Omicron’s rapid evolution. In August 2022, the Food and Drug Administration authorized booster shots targeting the then-dominant BA.5 Omicron variant. In September 2023, the agency authorized an XBB shot. But XBB is now in decline as a menagerie of even more evasive variants has evolved.
“Right now we are in a period of chaos,” said Marc Johnson, a virologist at the University of Missouri.
Several Omicron experts said the chaos could end soon. In August, a variant called BA.2.86 emerged with a host of new mutations – likely the result, again, of evolution taking place in an immunocompromised person.
At first, BA.2.86 did not seem to live up to its genetic potential, failing to spread quickly. “If genetics were all that mattered, it would have had its own Greek letter,” said Thomas Peacock, a virologist at the Pirbright Institute in Woking, England. “But BA.2.86 was a bit of a damp squib.”
However, in recent months, the BA.2.86 lineage appears to have shifted into high gear, gaining a mutation that allows it to evade even more antibodies. JN.1, as this mutated form is called, has become the most resistant version of the coronavirus. It seems to be growing rapidly in France and could soon spread to other countries.
It is difficult to predict the future evolution of a new variant like JN.1. Its success will depend on the type of immune defenses it encounters during its spread from host to host. At the start of the pandemic, things were simpler because no one had developed immunity to the coronavirus.
“At first we were just a big kindergarten,” said Michael Lässig, an evolutionary biologist at the University of Cologne.
Today, in contrast, most people on Earth have immunity in one form or another, whether from natural infection, vaccination, or both. “The virus sees a much more complex ecosystem,” said Dr. Lässig.
This global immunity means a smaller proportion of people will die than at the start of the pandemic. Omicron’s balance sheet nevertheless remains heavy. The US Centers for Disease Control and Prevention found that between October 2022 and September 2023, more than 80,000 people died from Covid, more than eight times as many as died from the flu.
As Omicron continues to evolve, epidemiologists still see an advantage to vaccinations. Justin Lessler, a researcher at the University of North Carolina, and colleagues recently carried out a projection of future Covid infections and concluded that annual vaccination campaigns could save up to 49,000 lives per year.
These vaccines will be more effective if they are updated to follow the evolution of the virus. But Katrina Lythgoe, a biologist at the University of Oxford, fears their development will slow as governments stop funding genetic sequencing of new variants.
“If we don’t order things, we won’t see them,” she said.
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