The Middletown Press (Middletown, CT)
Virus followed complex path to state
The distinct genetic mutation of the coronavirus that tore through Connecticut came from Europe via New York and is now the dominant mutation in the world.
But the first coronavirus cases that hit the state were genetically related to the virus that came from China through Washington state.
“This was of course before the international travel bans were enforced,” said Mary Petrone, a doctoral student at the Yale School of Public Health in the department of epidemiology of microbial diseases.
Petrone is part of a team of
researchers tracking the genetic mutations of the virus, building family trees — called phylogenetic trees — that can show how the virus has progressed around the world, community to community.
While there are some important caveats, she said the research could help public health experts in Connecticut better understand how to implement statewide and even local control measures.
“If you’re the mayor of New Haven, you’d want to know, are we getting viruses coming in from New York City, because people will take the rail line down there quite often, or are we getting virus coming in from Hartford, because that’s another major city in the state?” Petrone said. “And if you know that, then you can figure out the best way to sort of target your surveillance systems and target your control efforts.”
Mutation matters
All viruses mutate. Some mutations are good from the perspective of the virus — they help the virus produce more of itself — some are detrimental to the development of the virus and some are neutral, neither good or bad for the virus itself.
It’s referred to, as Richard Martinello explained, as the “fitness” of the virus.
“They’re just always mutating,” said Martinello, associate professor in the Department of Internal Medicine and Pediatrics at the Yale School of Medicine. “We are vastly outnumbered by these viruses. There’s billions of trillions of viruses, they’re replicating in people’s bodies quite a bit. And each time that virus replicates, there’s an opportunity for mutation.”
In some cases, mutations can help the virus get from one host to another. For example, the version of the virus that spread through New York and Connecticut in the spring is now the dominant strain in the world, Petrone said, making up more than half of all infections.
“It’s increasing in prevalence throughout the world,” she said. “I think now it’s 70 percent of the genomes that have been sequenced from June or
from May, now have this mutation.”
That strain of the virus appears to be very good at infecting humans.
“There are cases where we see, for example, one mutation or one lineage or one strain, as defined by a single mutation taking over the virus population, and that is, in fact, what we’ve seen with this specific mutation,” Petrone said. “And there has been some evidence to show that this mutation does increase the infectivity or the virus’ ability to infect human cells.”
Specifically, Martinello explained that the mutation affected the “spike protein,” the part of the virus that sticks to human cells.
“There’s some work suggesting that the virus with that mutation can actually stick better and get into the cell more readily than virus that does not have that particular mutation,” he said. “It may be more contagious because once it gets inside somebody’s body, it has a better chance of actually causing an infection, because it sticks better to the cells it wants to infect and, because of that, maybe that’s why we’re seeing it dominate.”
Though it may be better
at infecting human cells, at least in the lab, there’s no indication that this mutation, though dominant, is making people sicker.
“There doesn’t seem to be evidence that there is clinical difference in clinical outcomes if you get one versus the other,” Petrone said.
Viral detectives
Patrone and her colleagues have done genomic sequencing on thousands of viral samples, allowing them to understand the progression of the virus as it mutates.
This is helped, in part, by the fact that the coronavirus is built on RNA, as opposed to DNA.
“Viruses that are based in RNA, rather than DNA, actually mutate at a faster rate,” Martinello explained. “The DNA viruses, like the herpes viruses for example, they mutate also, of course. But the RNA viruses tend to to mutate more quickly because as they get reproduced, the error-checking mechanisms are oftentimes just absent or are very rudimentary compared to more complex microbes.”
This speed of mutation has allowed researchers, as Martinello said, to “take advantage of that mutation
frequency to better understand how viruses are being transmitted.”
“They can actually look at samples from Wuhan, China, from Milan, Italy, from New York City, and they can compare those sequences, and they know that there is a certain rate of mutations that they would expect,” he said. “And as those mutations accumulate within the virus, they can actually follow those patterns of mutations and use computer-based algorithms to try to medically reassemble how the viruses evolved over time, but also to understand how viruses may have been brought from one area of the world to another area of the world by people.”
What mutations don’t say
Tracking genetic mutations of a virus like the coronavirus is not, however, similar to contact tracing. You can’t know what viral mutation one individual patient passed to another individual patient, Petrone explained.
She called them “consensus genomes.”
“It’s not that you’ve just taken a nasopharyngeal swab from someone and pulled a virus out of there and said, ‘this is the virus.’
You’re basically making an abstraction of the viral population,” she said. “These phylogenetic trees are showing the evolutionary relationship between these consensus genomes, they’re not directly telling us about transmission. They’re not directly telling us about who infected whom.”
Researchers also can’t tell which mutations are specifically more transmissible or more virulent than any others. There are too many other factors to consider, Petrone said, like social distancing measures and the use of masks.
“Studies show that this particular strain seems to do a better job of infecting human cells,” she said. “But just because a virus can infect cells better, that doesn’t necessarily tell you about what’s happening on a human-to-human scale. Because you’re just thinking about, can the virus get in — yes or no. There’s a lot of other things that go along with the actual transmission process.”
And though Petrone and her team can drill down to the community level, the research only tracks virus mutations, not the people who carry the virus. She can’t say for certainty how a virus got to one place or another.
“What our findings don’t show is that someone from Washington state got on a plane and arrived in JFK, arrived in Hartford airport, and then infected people in Connecticut,” she said. “We don’t know if there are any intermediate steps there.”