On March 22, the World Health Organization announced that the omikron subvariant BA.2 had become the dominant form of SARS-CoV-2, the virus that causes Covid, worldwide. BA.2 bears many genetic similarities to its close relative BA.1, which has caused a global uptick in covid infections in recent months. But BA.2 is 30 to 50 percent more contagious than BA.1.
With this latest version of SARS-CoV-2 sweeping the planet, people fearing a pandemic everywhere are asking the same question: Is society doomed to face a succession of new virus variants, each more contagious than the next?
“We still don’t know the full ability of this virus to evolve and create radically new variants,” said Jeffrey Shaman, an infectious disease modeling expert at Columbia University’s School of Public Health. According to Shaman and other scientists, SARS-CoV-2 still has a lot of genetic leeway in how it infects human cells and evades the immune system† New variants can arise through stepwise changes in the virus sequence. But heavily mutated versions of SARS-CoV-2 that bear little resemblance to their predecessors “also came out of nowhere,” said Ralph Baric, a virologist at the University of North Carolina at Chapel Hill. “And if one of these variants is better at infecting cells or evading immunity than their predecessors, you’ll see increased transmission over the strains that came before that.”
The omikron subvariants were all discovered around the same time last November in South Africa. This new and drastically different versions of SARS-CoV-2 were shocking to many scientists, who had expected that the next major variant would incrementally descend from the delta variant. BA.1 quickly surpassed delta as the dominant strain worldwide, while BA.2 lagged, “probably in a rural area where it initially didn’t have much of a chance of spreading,” says computational biologist Bette Korber who studies viral diseases at Los Alamos National Laboratory in New Mexico. But after BA.2 got into larger, more interconnected communities, “it started to spread quickly.” As soon as it could jump to other countries, BA.2 exploded in Africa, Europe and Asia, and it currently accounts for nearly 55 percent of all new SARS-CoV-2 infections in the US, according to the latest data from the Centers for Disease Control and Prevention.
In the most likely scenario, BA.1, BA.2 and a third omikron subvariant that never got off the ground – BA.3 – evolved in a small population of immunocompromised humans. Stephen Griffin, a virologist at the University of Leeds School of Medicine in England, says the bouncing back and forth between members of this population likely provided ‘a training ground for the virus’, allowing SARS-CoV-2 to try out new mutations and testing and allowing it to spread more efficiently.
BA.1 has 60 mutations not found in the ancestral SARS-CoV-2 that first emerged in Wuhan, China. Among them are 32 genetic changes that are specifically in the virus’s iconic spike protein, which is a target for immune cells and vaccines. BA.2 shares many of the same mutations, but also has 28 unique genetic changes of its own, four of which are in the spike protein.
According to Baric, Omikron is the first SARS-CoV-2 variant to evolve in the context of increasing immunity in the population – the result of vaccines and previous infections with other forms of the virus. Earlier variants, namely alpha, beta, gamma and delta, competed for dominance mainly based on the extent to which they infected human cells in high numbers and moved efficiently among humans. But omikron gained the further advantage of being able to resist immune defenses to the earlier variants, increasing the number of susceptible people in the population.
The difference in neutralizing antibody responses to omikron, compared to previous variants, “is enormous,” says Baric. Neutralizing antibodies prevent SARS-CoV-2 from binding to ACE2 receptors, the virus’s gateway to human cells. “We’re talking about a 15- to 50-fold drop in antibody levels, depending on who’s doing the test and how recently you’ve been infected or boosted,” says Baric.
Identifying the mutations that allow omikron to ‘escape’ neutralizing antibodies is now the subject of intense research. At least some of these mutations appear to affect parts of the spike protein that bind to ACE2. In the ancestral virus, these mutations would have hindered the microbe’s ability to initiate an infection. But omikron seems to tolerate the changes without losing its ability to bind to ACE2. Ram Sasisekharan, a biological engineer at the Massachusetts Institute of Technology, says that as long as these mutations persist in the virus, “we can expect that omikron-like variants will continue to emerge, driven primarily by immune evasion rather than enhanced intrinsic contagiousness†
But contagiousness and immune evasion are also closely intertwined, and determining their respective roles in the spread of the virus is an extraordinary challenge. This is especially true at the current stage of the pandemic. Dozens of vaccines have been deployed against SARS-CoV-2, and countless forms of the virus have swept the world. Infections and vaccines contribute to immunity through a dizzying array of combinations, and “all of this is getting more and more messy for the scientific community to sort out,” says Baric.
Fortunately, there is so far evidence that the disease symptoms caused by BA.2 are no more severe than those caused by BA.1 in vaccinated people or people previously infected with SARS-CoV-2, Sasisekharan said.
BA.1 has clearly beaten delta, largely due to its ability to escape the immune system. But to what extent does immunity from a previous infection with BA.1 protect against BA.2?
The first indications suggest that reinfections with BA.2 after BA.1 occur, but are rare. “If you were infected with BA.1, you are probably well protected against BA.2,” says Griffin. “But the protection is not complete.” Scientists expect that places where BA.1 has already had a high peak, later peaks of BA.2 can occur. The BA.1 peak in South Africa declined rapidly last December, and BA.2 is “not much of a problem there,” said Juliet Pulliam, an epidemiologist at the DSI-NRF Center of Excellence in Epidemiological Modeling and Analysis. at South African Stellenbosch University. “Our numbers of cases are quite low at the moment.”
Experts are closely following the trajectory of BA.2 in the US, where BA.1 was also thriving earlier this year. The number of covid cases in this country has fallen by 35 percent in recent weeks, even as BA.2 has become the dominant strain. In parts of the US, including some states in the northeast, the number of SARS-CoV-2 infections is rising. But whether a national increase will follow is unknown. ‘We are now in a gray area,’ says Baric.
Other factors also determine the transmission of BA.2: vaccination and booster rates, public health measures and the average age of the population all play a role. The dramatic rise in BA.2 cases in Hong Kong is partly attributed to the hesitancy of the elderly to vaccinate. John Moore, a virologist at Weill Cornell Medicine College at Cornell University, believes BA.2 has surged in European countries and the UK, mainly due to the relaxation of Covid restrictions. “The governments in those countries, especially the UK, said, ‘Covid is over, let’s party,’ he says. “That’s exactly what a highly transferable variant needs.”
If the succession of more and more transmissible variants has a bright spot, it is that they evolve in tandem with the immunity of the population. Each new variant may cause fewer deaths simply because more people are able to avoid infection and serious illness. But Shaman points out that SARS-CoV-2 is also much more susceptible to change than the other respiratory viruses we’ve learned to live with. The transmissibility of new SARS-CoV-2 variants should eventually reach a plateau, much like the coronaviruses that cause the common cold. But in the meantime, “we don’t know what the next decade will look like with this virus,” Shaman says. “So we have to keep an eye on it.”