XBB.1.5, BA.2.86, JN.1: How to understand the Covid-19 alphabet soup

The virus that causes Covid-19 has more letters to describe its many derivatives than a bowl of alphabet soup.

Omicron and Delta were names for the coronavirus that people quickly learned and used in the height of the pandemic. But at this point, most non-scientists probably could not name the version of the virus that’s set to become the next dominant one around the world. (It’s JN.1, by the way.)

Although the common cold doesn’t get as many names – at least not the ones that make headlines – the specificity with which scientists talk about SARS-CoV-2, the virus that causes Covid-19, matters because it is still such a problem.

A virus like this one has a lot of different names because it is changing constantly, and scientists need a common language to talk about a specific version that they’re seeing in a particular community or that they’re working with to develop treatments, vaccines and tests.

“Bob the Virus” or “Susan the Variant” would probably be easier to remember than BA.2.86, the ancestor of JN.1. But the people who decide how to name infectious diseases and viruses wanted to get away from an old tradition of naming a virus for the animal it was first sequenced in, as with the virus formerly known as monkeypox, or for the place where it was discovered, like the hemorrhagic fever called the Marburg virus, named after the West German town of Marburg an der Lahn.

In 2015, the World Health Organization decided that naming a new human infectious disease for a person, place or thing could be stigmatizing and have unintended negative consequences. For example, when a H1N1 virus that infected pigs, birds and humans was called “swine flu” during the 2009-10 flu season, sales of pork in the US declined, and hundreds of thousands of pigs were killed unnecessarily in places like Egypt even though the virus did not spread through eating pork.

The virus that causes Covid-19 started off as the Wuhan coronavirus because the illness was first identified in Wuhan, China, in February 2020. The International Committee on Taxonomy of Viruses called it SARS-CoV-2, shorthand for “severe acute respiratory syndrome coronavirus 2.” The team picked the name because although the new virus is different, it is genetically related to the coronavirus that caused the 2003 outbreak of SARS.

WHO wanted to refer to it as “the virus responsible for Covid-19” because it said at the time that using the name SARS “can have unintended consequences” and create “unnecessary fear of some populations, especially in Asia which was worst affected by the SARS outbreak in 2003.” WHO named the disease caused by the virus Covid-19, which is shorthand for “coronavirus disease of 2019,” the year it was first detected.

But because scientists need to speak with specificity about the virus’ offspring and because viruses change quickly, at least on a human timeframe, there can be a lot more names involved.

In March 2020, scientists who were sequencing the virus’ genome to figure out how it was evolving were calling the same variations by different names depending on the lab. Researchers decided to devise a way for everyone to use the same names, so they developed a naming system called Pango or Pangolin, which stands for phylogenetic assignment of named global outbreak lineage.

“This system Pangolin was developed in 2020, when it became clear that Covid was going to be a global problem,” said Dr. Kurt Williamson, an associate professor in the biology department at William & Mary.

Viruses change so quickly in part because the way they reproduce involves what’s called RNA polymerase. To make a copy of a cell, the human body uses DNA polymerase, which has what Williamson says is a really good proofreading function that can check and fix mistakes. RNA polymerase doesn’t have that proofreading capability, so it makes mistakes much more frequently and generates much greater variation more quickly relative to the human timeframe.

The other way viruses change involves lineages, a group of closely related viruses with a common ancestor. When two lineages both infect one cell at the same time, the RNA polymerase can do something called “template switching” while it’s copying one viral genome to make a new virus.

“It can basically switch between using one virus to make a copy and then switch to the genome of the other version of the virus to finish making a copy, which is really weird, but that leads to what are called recombinant,” Williamson said. “You’ve basically taken features of two different viruses and combine them now into one offspring that can, when it copies its genome, it’s going to make copies with that new combination. That creates issues with keeping track of all the different versions.”

At the start of the pandemic, there were only two main lineages of SARS-CoV-2: A and B. When these lineages mutated, Pango named each sublineage, a term used to define a lineage as it relates to being a direct descendant of a parent lineage. B.1.1.7, for instance, is the seventh variant of the B.1.1 subvariant, which was the first subvariant of B.1.

Eventually, then, came C and D and so on as the virus continues to make new variants through drift mutations, a mistake while copying, and recombination through template switching.

“So for scientists to talk to each other, we use this decidedly unsexy but precise way of talking about it. Which variant from which lineage? Is it in A lineage? Is it a B lineage? Is it a C lineage? And so on. And then when you have like the X, like XBB.1.5, the X denotes that it’s a recombinant,” Williamson said.

“It’s clunky,” he added. “But it does make its way into public communication.”

That kind of “Who’s on first? What’s on second?” sense of order in naming may make sense to scientists who need to know every minute change, but it quickly became too complicated for the general public, and so some people started using slightly more familiar terms like the “Kent variant” for B.1.1.7, which was named for where it was sequenced.

In May 2021, to get away from the stigma of naming a deadly virus for a place and to get away from the “clunkiness,” WHO came up with a simpler Greek letter system to name some of the variations. It didn’t replace Pango or any other scientific naming systems needed for more specific communications between scientists, but it would use these new designations only for variants that were significantly different from the original and that posed a different kind of threat to public health – what the agency called variants of interest or variants of concern. The “Kent variant,” or B.1.1.7, was renamed Alpha. B.1.617.2, first identified in India, became Delta, and so on.

WHO needed to distinguish between Delta and the Omicron strain because the differences in the virus were so dramatic that it was affecting its behavior, and our immune systems barely recognized the new version of the virus, leading to new waves of infections, hospitalizations and deaths. WHO needed to be able to talk about those differences.

At the time, there was also a second Omicron strain, BA.2, with dozens of new gene mutations that some argued deserved its own Greek letter. But that never happened. Instead, WHO created a new category of Omicron subvariants under monitoring to let people in public health know which of the spinoffs should be watched.

Scientists also use other classification systems to describe the similarities and differences between the viruses they study.

There’s also Nextclade, a tool used to classify virus sequences according to how they are genetically related. Not every version of the virus gets its own clade, but members of a clade will share similar features because of a common ancestry. That system uses a two-digit year followed by a letter given in order of assignment for that year, so 22A is the first clade in 2022, for example.

“Even though we have what sounds kind of clunky to the public, it allows scientists to know exactly what the other person is talking about when they use that system to communicate, and it’s important,” Williamson said.

But there’s so much variation, he said, that discussion continues about establishing new rules to make naming simpler. The naming system might also have to change simply because there are so many variants that they will require too many letters, making things too complicated even for scientists to remember.

Although the general public shouldn’t have to worry about that level of specificity for Covid, Williamson says, members of the public could do their part to make things easier by reducing the coronavirus’ spread and the number of new variants.

Along with getting the Covid-19 vaccine, “simple things people can do like hand-washing, masking around high-risk people, or if you’re not feeling great, stay home. Those are pretty low-level things we all have the power to do,” he said.

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