What comes after Omicron? New variants are emerging.

Every few months for the first two years of the pandemic the public learned the name of a new coronavirus variant that had emerged and was more adept at infecting us or causing severe disease. Ten variants with Greek names—Alpha through Mu—killed millions. Then in November 2021, Omicron, a vastly different version of the virus emerged. For the past 10 months the World Health Organisation hasn’t named any new variants, which begs the question: Has the virus stopped evolving?

Infections over the last three months have been dominated by new sublineages of Omicron: BA.2, BA.2.12.1, BA.4., and BA.5. In the U.K., symptomatic infections have steadily increased since August 27—the day they hit lowest level this year—according to the ZOE COVID-19 study, an App-based project in which patients enter their symptoms on their phone. In the U.S., infection rates among U.S. nursing home residents have risen nine-fold since the end of April, and by August death rates almost quadrupled in this group, according to the data compiled by the AARP Public Policy Institute and the Scripps Gerontology Center at Miami University in Ohio. While WHO has not anointed any of these recent Omicron derivatives with a Greek letter of their own, experts fear these variants could undermine the new boosters and treatments, leading to a new wave of infections and deaths.

The coronavirus is continuously evolving and gaining novel mutations; to date there have been more than 200 newer Omicron sublineages and their derivatives. “SARS-CoV-2 evolution is not over,” says Olivier Schwartz, head of the Virus & Immunity Unit at Institut Pasteur, Paris.

Marion Koopmans, the director of the WHO Collaborating Center for emerging infectious diseases and a member of WHO’s mission to probe the origins of the COVID-19 pandemic says, “The situation is much better than it has been.” But she cautions that with fall and winter approaching, we should remain prepared for another substantial wave. “A marathon runner does not slow down before the finish line.”

SARS-CoV-2 variants are still evolving

Every time SARS-CoV-2, the virus that causes COVID-19, replicates during an infection, it can make mistakes and change a little bit. These changes, called mutations, are random and usually have no or little consequence for the virus. If the same mutation appears and spreads in unrelated populations, that suggests it offers an advantage to the virus. Those mutations then create a new branch of the SARS-CoV-2 evolutionary tree. The viruses that make up that branch are called "variants." 

“The more SARS-CoV-2 circulates, the more it may change,” says Maria Van Kerkhove, the epidemiologist who leads the COVID-19 response at WHO. Scientists also believe that Omicron like variants could evolve in people with compromised immune systems where the virus can persist longer while acquiring dozens of new mutations.

Some mutations can help a variant spread more easily or may cause more severe disease. Others can alter the appearance of the virus, enabling it to dodge immunity from previous infections or vaccines and making it more difficult to detect. These mutations can also render authorised therapies ineffective. When this happens, WHO labels the variant as interesting or concerning.

In May 2021, WHO began assigning variants of interest and variants of concern letters of the Greek alphabet. “But WHO does not name all variants,” says Anurag Agrawal, the chair of WHO’s Technical Advisory Group for Virus Evolution which makes recommendations on naming variants. “WHO only names a variant when it is concerned that additional risks are being created that require new public health action,” Agrawal explains.

Currently, all Omicron sublineages are considered variants of concern because they share similar characteristics: They spread more easily than earlier variants and can dodge previous immunity. But fortunately, infection from one Omicron subvariant still sufficiently reduces the risk of getting reinfected with another. The subvariants also don’t seem to pose greater risks that the parent Omicron, says Van Kerkhove.

Omicron variants show evolutionary leaps

The emergence of Omicron less than one year ago represented a big shift in SARS-CoV-2 evolution. More than half of COVID-19 infections worldwide since November 2021 were most likely caused by one of the five Omicron subvariants: BA.1, BA.2, BA.3, BA.4 and BA.5. With Omicron’s ability to dodge immunity from previous variants, it has prompted scientists, including Schwartz, to suggest that Omicron could even be considered a distinct SARS-CoV-2 serotype—a virus that is so different from previous variants that antibodies generated against one do not protect sufficiently against the other. For example, flu virus has three serotypes: influenza A, B, and C.

In the last few months Omicron BA.2 has spawned a series of variants including BA.2.75, BA.2.10.4, BJ.1, and BS.1. These variants, some carrying dozens of new mutations, are so different from parental variant BA.2 that scientists call them “second generation” variants. A second-generation variant represents a large evolutionary jump from previous variant lineages without small intermediate steps.

On the evolutionary scale, the newly spreading variants, such as BA.2.75 are more different from the original Omicron than Alpha, Beta, Gamma, and Delta were from the ancestral strains, says Thomas Peacock, a virologist at Imperial College London. All the mutations in these early variants look minor compared to Omicron and its subvariants, says Peacock.

“One potentially worrisome subvariant is BA.2.75.2, which carries additional mutations compared to BA.2.75 and seems to be particularly resistant to antibodies,” says Schwartz.

While WHO may not have given these new variants a Greek letter name, Yunlong (Richard) Cao, an immunologist at Peking University in Beijing says, “It's definitely inappropriate to say there have been no new variants since November 2021.”

BA.5 is currently predominant in many countries, and BA.2.75 in others. They are both able to escape the immune systems of people who have been vaccinated and or suffered an infection, although current vaccines may still hold good.

“What we are seeing now is that evolution is continuing,” Koopmans says. This is what you would expect when there is the combination of substantial circulation and greater acquired immunity. “So we do expect further escape variants,” she adds.

There is an ongoing debate about how useful it is to lump all Omicron subvariants together. Although the Omicron lineages BA.1, BA.2, and BA.5 were close enough to be called Omicron, some scientists think that the new variants are distinctive enough that they could be given a new Greek letter name.

“Some of these new viruses are as genetically distinct as the original variants so it remains unclear how helpful it is thinking of them as Omicron still,” Peacock says.

WHO’s task force disagrees. “If any variant or subvariant is determined to be significantly different than other variants or subvariants of Omicron, they will be assigned a new name,” says Van Kerkhove. “But right now, all of these subvariants are considered Omicron, all are variants of concern, and all require enhanced actions in countries.”

As there is no reliable human data to indicate that the new Omicron subvariants are more severe than others, says Agrawal, the public health advice remains the same.

In the meantime, early diagnosis, early clinical care, appropriate use of available therapeutics, and vaccination are needed to reduce the spread of the virus and reduce the chance of new variants emerging, says Van Kerkhove. “We can live with COVID-19 responsibly and take simple measures to reduce the spread, such as distancing, masking, ventilation, cleaning hands, staying home if unwell.”