covid-19

What We Know About All the Omicron Subvariants

Including BA.2.12.1, BA.4, and BA.5.

Photo-Illustration: Intelligencer; Photos: Getty Images
Photo-Illustration: Intelligencer; Photos: Getty Images

Whether you’re paying attention to the latest phase of the pandemic or not, the coronavirus is still evolving, and the subvariants are starting to add up. There are now at least four Omicron subvariants circulating in the country. BA.2, which has already driven the rise in cases across much of the U.S., is still the dominant strain — but barely. BA.2.12.1 will soon make up a majority of U.S. cases, as it appears to be even more transmissible than its COVID ancestors, as do the newest strains now circulating in America: BA.4 and BA.5. Below is a primer on everything Omicron and what impact its sublineages may have.

All COVID is now a sublineage of Omicron.

With the Delta variant effectively burned out in most of the world, the remaining variants all trace their lineage through Omicron, as this tracker shows:

At this point, the original Omicron strain known as BA.1 — which caused the U.S. to clock over 1 million confirmed cases in a single day in January — has been overtaken by its successors, each of which has proven more transmissible than the original. As of the week ending May 7, subvariants of BA.1 — BA.1.1 and BA.1.1529 — were estimated to make up fewer than 1 percent of all new U.S. cases.

BA.2

First detected in the U.S. in January, the BA.2 subvariant quickly became the dominant strain in America, overtaking BA.1 by late March, according to the CDC. Consideredroughly 1.5 times more transmissible than the original, the variant — known as “stealth Omicron” for its difficulty to be differentiated in PCR tests — caused a slight increase in confirmed COVID cases in early April. By mid-April, BA.2 represented close to 90 percent of new U.S. cases. Thankfully, BA.2 does not appear to have caused another severe Omicron wave, in part because of a level of protection for those previously infected with BA.1 — but the number of U.S. cases has still continued to rise.

BA.2.12 and BA.2.12.1

Two closely related subvariants, known as BA.2.12 and BA.2.12.1, recently began spreading in the U.S. BA.2.12.1 has a mutation on the part of the spike protein of the virus that binds with human cells, and initial research indicates it may be around 25 percent more transmissible than BA.2. In late April, it made up around 29 percent of U.S. cases; then nearly 43 percent as of the week ending May 7.

U.S. variant proportions as of the week ending May 7. Illustration: CDC/Handout

BA.2.12.1 is already the most dominant COVID strain in much of the northeast, including New York and New Jersey, and it is soon expected to replace BA.2 as the most dominant strain in the country overall.

Map of U.S. variant proportions, by region, as of the week ending May 7. Illustration: CDC/Handout

BA.4 and BA.5

Last month, scientists in South Africa identified two new Omicron sublineages, BA.4 and BA.5, which seem to be more infectious than BA.2, may be better equipped with immunity escape, and appear to be driving a surge of new cases in the country. Genomic surveillance has indicated that as of April 20, BA.4 and BA.5 made up more than 70 percent of new cases in South Africa. Experts there now expect a fifth COVID wave, even though an estimated 90 percent of the population is estimated to have some level of immunity to COVID from either vaccination or prior infection. Thus far, the surge in cases has not led to a surge in hospitalizations. And there is no evidence — at least yet — that the strains are likely to lead to more severe disease than previous strains.

That’s the good news. What’s worrisome about BA.4 and BA.5 is that preliminary data suggests the subvariants have mutations that, according to recent South African research, equip them with “extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both.” The researchers conclude that “based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.”

Small numbers of BA.4 and BA.5 cases have been detected in at least 20 other countries, including handfuls of cases of each strain in the U.S. — though there is no evidence they are circulating widely here yet. It’s not clear whether other nations will face surges from the two strains as South Africa is experiencing.

Can you be infected with these subvariants if you already had Omicron (BA.1)?

That does appear to be possible with BA.4 and BA.5, based on early data from South Africa, and might be possible with the BA.2.12 lineages as well.

What about recombinant strains?

Thankfully, recombinant strains of the virus — think super-mutants combining the transmissibility of an Omicron subvariant with the severity of Delta — have been rare. As computational biologist Cornelius Roemer explains, this is because “there was never much co-circulation of the two lineages. When BA.2 grew large, Delta was already gone.” (He does warn that the countries that did have co-circulation don’t sequence the virus as frequently as in the U.S. and Europe, “so even if recombinants existed, it would take a while until we see them in published sequences.”)

In the United Kingdom, a “Frankenstein variant” combining BA.1 and BA.2 known as XE has been sequenced, with 1,125 cases identified in the country by early April. And while cases have been reported in India and Japan, it does not appear to be significantly more transmissible than BA.2 and never took over as the dominant strain in the U.K. “It is the devil we know, so to speak,” Case Western Reserve University immunologist Mark Cameron told CNBC. “Essentially a reshuffling of the same deck of cards.”

What is the Biden administration doing to prepare?

At his first news briefing as the new White House COVID-response coordinator in late April, Dr. Ashish Jha provided an apt summary for the Biden administration’s approach to the latest stage of the pandemic. “We have a very, very contagious variant out there,” he said on the day the vice-president tested positive for COVID. “It is going to be hard to ensure that no one gets COVID in America. That’s not even a policy goal.”

The rise of Omicron subvariants has coincided with the Biden administration’s shift to treat COVID as an endemic virus, a reaction that has involved cutting funding requests despite all the unknown variables of the strains ahead. In early March, the White House cut $12 billion from its request to Congress for supplies including tests, therapeutics, and vaccines because the spending would need the co-sign of at least ten Republicans. Eventually, the COVID funding bill approved by Congress was slashed by another $12 billion, leaving the country short for future vaccination programs. According to the Kaiser Family Foundation, the administration barely has just enough doses to give a second booster to 70 percent of Americans over 50 — a group that has already been cleared to get follow-up boosters. With no more federal funding for vaccinations and tests for the uninsured, many providers aren’t offering shots and swabs for Americans without health insurance anymore. Another substantial deficit in the bill: It has no funding for vaccination and testing abroad despite repeated warnings from public-health experts that the continued spread of the virus would lead to more variants, thereby extending the pandemic.

Can we slow down the subvariant evolution?

Alpha, Beta, Delta, and several Omicron variants have swept through the world, causing tens of millions of cases and millions of deaths since vaccines became widely available in many parts of the world. According to epidemiologist Michael Osterholm, the director of the Center for Infectious Disease Research and Policy at the University of Minnesota and a member of the Biden administration’s COVID-19 Advisory Board, the intense pace of change is directly related to the speed at which the novel virus has spread. “In the early days of the pandemic, remember there were many fewer people who were infected, and you have to be infected to drive the genetic changes of the virus,” he says. “Kind of like compound interest, as more and more people got infected, more and more opportunities occurred for the virus to go through various mutations. That by itself helped drive it.”

As for slowing the rate of evolving variants, the answer is as simple as it is hard to attain. “There is one way, and it’s to stop transmission,” says Osterholm. “If the virus is not reproducing itself, we wouldn’t see nearly the same level of mutational changes.”

This post has been updated.

What We Know About All the Omicron Subvariants