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) infected millions. Then in November 2021, Omicron, a vastly different version of the virus emerged. For the past 10 months the World Health Organization hasn’t named any new variants, which begs the question: Has the virus stopped evolving?

At least 300 Americans have died from COVID-19 every day for the past three months and roughly 50,000 new COVID-19 infections were reported in the U.S. every day in September–all caused by new sublineages of Omicron: BA.2, BA.2. 12.1, BA.4., and BA.5. 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. In the United Kingdom, often a harbinger of COVID-19 trends in the U.S., 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. Experts worry that these Omicron derivatives could cause new infections and death. Although WHO has not anointed these Omicron derivatives with a Greek letters, experts are concerned about the potential for them to undermine new boosters and treatments.

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

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 mutations, also known as mutations, can occur at random and have little or no consequence for the virus. The virus may have an advantage if the same mutation occurs in different populations. These mutations create a new branch in the SARS-CoV-2 evolutionary tree. “Variants” are the viruses that make up this branch.

“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 virus’ appearance, making it harder to detect and evade previous vaccines or immunity. These mutations can also make it impossible to use approved therapies. WHO will label the variant as concerning or interesting when this happens.

In May 2021, WHO began assigning variants of interest and variants of concern letters of the Greek alphabet. Anurag Agrawal (chair of WHO’s Technical Advisory Group for Virus Evolution), who makes recommendations about naming variants, says that “But WHO doesn’t name all variants.” Agrawal explained that WHO names variants only when it is concerned about the creation of new risks that will require public health action.

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. However, the risk of being infected by an Omicron subvariant is still low enough to avoid reinfection with another. Van Kerkhove says that subvariants don’t pose any greater risk than the parent Omicron.

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 is a significant evolutionary leap from previous variant lineages, without any 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. Peacock says that all the mutations in these early variants are minor when compared to Omicron or its subvariants.

“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 if there is substantial circulation and greater acquired immunity. She adds, “So we do anticipate further escape variants.”

There is an ongoing debate about how useful it is to lump all Omicron subvariants together. Omicron lineages BA.1, BA.2, BA.5, and BA.5 were close enough for Omicron to be called Omicron. However, some scientists believe that the new variants could be given a 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. Van Kerkhove states that if any subvariant or variant is found to be significantly different from other Omicron variants or subvariants, they will be given a new name. “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.”