Late in 2019, likely somewhere in the Chinese city of Wuhan, what would come to be called the SARS-CoV-2 coronavirus infected its first human being — and began replicating.
By the time the year was out, the genetic family tree of that original virus’ descendants had already split into two branches. Once settled into Europe, the tree branched further. And by the time the first case of COVID-19 was identified in Colorado in March, there were at least six separate, genetically differentiated branches of coronavirus variants — known as clades — spreading worldwide, according to the virus-tracking website Nextstrain.
There are now even more branches, at least 12, containing potentially hundreds of variants of the pandemic-causing virus, according to Nextstrain’s analysis. And that understanding of the virus’ lineage is crucial to placing into context news of worrisome new variants that have been detected in Colorado, state public health officials say.
Variants are expected. It’s what those variants do that is important.
“It’s not a surprise that the virus is changing as it moves through the population,” said Emily Travanty, who holds a PhD in microbiology and is the interim director of the state’s public health lab. “It’s going to change and mutate. And some of these mutations could have impacts on health and transmission and, potentially, even on disease course.”
Clades and variants, explained
To understand how scientists talk about virus mutations, it helps to speak a bit of the language: clade and variant. To do that, we’re going to ask you to think of a golden retriever. Like this one.
With apologies to virologists for the oversimplification, this golden retriever is a variant — a sub-subcategory of dog that is somewhat genetically distinct from other domesticated dogs but not so distinct that it’s no longer a dog. Zoom out one level and you’ve reached a clade — the subcategory that contains a group of similar variants. (In our metaphor, the clade would include all retrievers).
The term “strain” is a little less well-defined. Travanty said she thinks of it as an even larger category that contains multiple clades, though there is some dispute about this.
Nextstrain, which collects and maps genetic information from virus samples taken across the globe, names clades with numbers and letters based on the year and order in which they were identified. So the first clade of SARS-Cov-2 — the virus that causes COVID-19 — was 19A, then 19B, 20A and so on. They’re up to 20J, currently.
Since the beginning of the pandemic, Colorado has seen cases from variants belonging to at least five clades, according to Nextstrain: 20A, 20B, 20C, 20G and 20I.
The first viral samples examined in the state came from clade 20A, which grew to prominence in Europe. By summer, Colorado saw a number of cases in clade 20C, another clade that arose in Europe and popped up in American outbreaks. By the surge of late-fall, though, Colorado’s cases — like much of the rest of the country’s — belonged to clade 20G, a clade mainly reported in North America.
To Travanty, this shows how the virus changed as travel restrictions lingered.
“I do think we are seeing more geographic isolation in these clades because travel has been so tamped down,” she said.
There’s a caveat to this historical narrative, though. You can’t identify which clade a case belongs to based on the standard coronavirus test. Those tests are simply searching for the presence of the virus, regardless of its subcategory.
Categorizing a case based on clade requires genetic sequencing of the virus in the sample. The state public health lab is one of dozens of labs uploading sequencing information to Nextstrain to create SAR-CoV-2’s family tree.
Currently, the state is able to sequence 300 samples a week, Travanty said. But that capacity was a lot less at the beginning of the pandemic, making the analysis from that period a little murky.
“The total number of overall samples in the beginning were maybe not as representative of everything that was circulating at the time,” Travanty said.
When to get worried
Viruses, by their nature, mutate. But coronaviruses are notable for how much they don’t mutate.
Coronaviruses have proofreading mechanisms in their genetic code to stamp out errors during replication — errors often being things that hinder the virus’ ability to spread. But given how many people the SARS-CoV-2 virus has infected, mutations are to be expected. Travanty said SARS-CoV-2 picks up about two mutations a month as it replicates and jumps from person to person. And some of those mutations are things that make the virus more dangerous.
“A variant of interest would be when you see a specific mutation in a part of the genome that we know is important,” Travanty said.
This is where the “variants of concern” come in. These variants — like ones first identified in the United Kingdom, South Africa and Brazil — have mutations that might make them more transmissible.
“They seem to have a stronger binding affinity to human cells … meaning that they are essentially a little more sticky,” Dr. Rachel Herlihy, the state epidemiologist, said. “So the virus sticks more strongly to human cells.”
Colorado has so far identified 67 cases of “variants of concern” in the state. Most prominent among these is the U.K. variant, known scientifically as B.1.1.7. The variant is part of clade 20I.
Herlihy said the variants still make up a small percentage of overall cases and “at this point, we’re really not seeing any clear trend.”
But, regardless of the variant, the playbook remains the same: social distancing, mask-wearing and hand-washing.
“The strategies that we’ve been using in the last couple of months,” Herlihy said, “are really the same strategies that are going to be effective at decreasing transmission of the variant.”