nytimes.com 
<https://www.nytimes.com/2020/04/08/science/new-york-coronavirus-cases-europe-genomes.html>
  


Most New York Coronavirus Cases Came From Europe, Genomes Show


By Carl Zimmer

10-12 minutes

  _____  

matter

Travelers seeded multiple cases starting as early as mid-February, genomes show.

 

Credit...National Institutes of Health/EPA, via Shutterstock

New research indicates that the coronavirus began to circulate in the New York 
area by mid-February, weeks before the first confirmed case, and that travelers 
brought in the virus mainly from Europe, not Asia.

“The majority is clearly European,” said Harm van Bakel, a geneticist at Icahn 
School of Medicine at Mount Sinai, who co-wrote a study awaiting peer review.

A separate team at N.Y.U. Grossman School of Medicine came to strikingly 
similar conclusions, despite studying a different group of cases. Both teams 
analyzed genomes from coronaviruses taken from New Yorkers starting in 
mid-March.

The research revealed a previously hidden spread of the virus that might have 
been detected if aggressive testing programs had been put in place.

On Jan. 31, President Trump barred foreign nationals from entering the country 
if they had been in China during the prior two weeks.

It would not be until late February that Italy would begin locking down towns 
and cities, and March 11 when Mr. Trump said he would block travelers from most 
European countries. But New Yorkers had already been traveling home with the 
virus <https://www.nytimes.com/2020/03/19/health/coronavirus-travel-ban.html> .

“People were just oblivious,” said Adriana Heguy, a member of the N.Y.U. team.

Dr. Heguy and Dr. van Bakel belong to an international guild of viral 
historians. They ferret out the history of outbreaks by poring over clues 
embedded in the genetic material of viruses taken from thousands of patients.

Viruses invade a cell and take over its molecular machinery, causing it to make 
new viruses.

The process is quick and sloppy. As a result, new viruses can gain a new 
mutation that wasn’t present in their ancestor. If a new virus manages to 
escape its host and infect other people, its descendants will inherit that 
mutation.

Tracking viral mutations demands sequencing all the genetic material in a virus 
— its genome. Once researchers have gathered the genomes from a number of virus 
samples, they can compare their mutations.

Sophisticated computer programs can then figure out how all of those mutations 
arose as viruses descended from a common ancestor. If they get enough data, 
they can make rough estimates about how long ago those ancestors lived. That’s 
because mutations arise at a roughly regular pace, like a molecular clock.

Maciej Boni of Penn State University and his colleagues recently used this 
method to see where the coronavirus, designated SARS-CoV-2, came from in the 
first place. While conspiracy theories might falsely claim the virus was 
concocted in a lab, the virus’s genome makes clear that it arose in bats 
<https://www.biorxiv.org/content/10.1101/2020.03.30.015008v1> .

There are many kinds of coronaviruses, which infect both humans and animals. 
Dr. Boni and his colleagues found that the genome of the new virus contains a 
number of mutations in common with strains of coronaviruses that infect bats.

The most closely related coronavirus is in a Chinese horseshoe bat, the 
researchers found. But the new virus has gained some unique mutations since 
splitting off from that bat virus decades ago.

Dr. Boni said that ancestral virus probably gave rise to a number of strains 
that infected horseshoe bats, and perhaps sometimes other animals.

“Very likely there’s a vast unsampled diversity,” he said.

Copying mistakes aren’t the only way for new viruses to arise. Sometimes two 
kinds of coronaviruses will infect the same cell. Their genetic material gets 
mixed up in new viruses.

It’s entirely possible, Dr. Boni said, in the past 10 or 20 years, a hybrid 
virus arose in some horseshoe bat that was well-suited to infect humans, too. 
Later, that virus somehow managed to cross the species barrier.

“Once in a while, one of these viruses wins the lottery,” he said.

In January, a team of Chinese and Australian researchers published the first 
genome of the new virus. Since then, researchers around the world have 
sequenced over 3,000 more. Some are genetically identical to each other, while 
others carry distinctive mutations.

That’s just a tiny sampling of the full diversity of the virus. As of April 8, 
there were 1.5 million confirmed cases 
<https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6>
  of Covid-19, and the true total is probably many millions more. But already, 
the genomes of the virus are revealing previously hidden outlines of its 
history over the past few months.

As new genomes come to light, researchers upload them to an online database 
called GISAID <https://www.gisaid.org/> . A team of virus evolution experts are 
analyzing the growing collection of genomes in a project called Nextstrain 
<https://nextstrain.org/> . They continually update the virus family tree.

The deepest branches of the tree all belong to lineages from China. The 
Nextstrain team has also used the mutation rate to determine that the virus 
probably first moved into humans from an animal host in late 2019. On Dec. 31, 
China announced that doctors in Wuhan were treating dozens of cases of a 
mysterious new respiratory illness.

In January, as the scope of the catastrophe in China became clear, a few 
countries started an aggressive testing program. They were able to track the 
arrival of the virus on their territory and track its spread through their 
populations.

But the United States fumbled in making its first diagnostic kits and initially 
limited testing only to people who had come from China and displayed symptoms 
of Covid-19.

“It was a disaster that we didn’t do testing,” Dr. Heguy said.

A few cases came to light starting at the end of January. But it was easy to 
dismiss them as rare imports that did not lead to local outbreaks.

The illusion was dashed at the end of February by Trevor Bedford, an associate 
professor at the Fred Hutchinson Cancer Research Center and the University of 
Washington, and his colleagues.

Using Nextstrain, they showed 
<https://www.nytimes.com/2020/03/01/health/coronavirus-washington-spread.html>  
that a virus identified in a patient in late February had mutation shared by 
one identified in Washington on Jan. 20.

The Washington viruses also shared other mutations in common with ones isolated 
in Wuhan, suggesting that a traveler had brought the coronavirus from China.

With that discovery, Dr. Bedford and his colleagues took the lead in sequencing 
coronavirus genomes. Sequencing more genomes around Washington gave them a 
better view of how the outbreak there got started.

“I’m quite confident that it was not spreading in December in the United 
States,” Dr. Bedford said. “There may have been a couple other introductions in 
January that didn’t take off in the same way.”

As new cases arose in other parts of the country, other researchers set up 
their own pipelines. The first positive test result in New York came on March 
1, and after a couple of weeks, patients surged into the city’s hospitals.

“I thought, ‘We need to do this for New York,’” Dr. Heguy said.

Dr. Heguy and her colleagues found some New York viruses that shared unique 
mutations not found elsewhere. “That’s when you know you’ve had a silent 
transmission for a while,” she said.

Dr. Heguy estimated that the virus began circulating in the New York area a 
couple of months ago.

And researchers at Mount Sinai started sequencing the genomes of patients 
coming through their hospital. They found that the earliest cases identified in 
New York were not linked to later ones.

“Two weeks later, we start seeing viruses related to each other,” said Ana 
Silvia Gonzalez-Reiche, a member of the Mount Sinai team.

Dr. Gonzalez-Reiche and her colleagues found that these viruses were 
practically identical to viruses found around Europe. They cannot say on what 
particular flight a particular virus arrived in New York. But they write that 
the viruses reveal “a period of untracked global transmission between late 
January to mid-February.”

So far, the Mount Sinai researchers have identified seven separate lineages of 
viruses that entered New York and began circulating. “We will probably find 
more,” Dr. van Bakel said.

The coronavirus genomes are also revealing hints of early cross-country travel.

Dr. van Bakel and his colleagues found one New York virus that was identical to 
one of the Washington viruses found by Dr. Bedford and his colleagues. In a 
separate study, <https://www.medrxiv.org/content/10.1101/2020.03.25.20043828v1> 
 researchers at Yale found another Washington-related virus. Combined, the two 
studies hint that the coronavirus has been moving from coast to coast for 
several weeks.

Sidney Bell, a computational biologist working with the Nextstrain team, 
cautions people not to read too much into these new mutations themselves. “Just 
because something is different doesn’t mean it matters,” Dr. Bell said.

Mutations do not automatically turn viruses into new, fearsome strains. They 
often don’t bring about any change at all. “To me, mutations are inevitable and 
kind of boring,” Dr. Bell said. “But in the movies, you get the X-Men.”

Peter Thielen, a virologist at the Applied Physics Laboratory at Johns Hopkins 
University, likes to think of the spread of viruses like a dandelion seed 
landing on an empty field.

The flower grows up and produces seeds of its own. Those seeds spread and 
sprout. New mutations arise over the generations as the dandelions fill the 
field. “But they’re all still dandelions,” Dr. Thielen said.

While the coronavirus mutations are useful for telling lineages apart, they 
don’t have any apparent effect on how the virus works.

That’s good news for scientists working on a vaccine.

Vaccine developers hope to fight Covid-19 by teaching our bodies to make 
antibodies that can grab onto the virus and block its entry into cells.

Some viruses evolve so quickly that they require vaccines that can produce 
several different antibodies. That’s not the case for Covid-19. Like other 
coronaviruses, it has a relatively slow mutation rate compared to some viruses, 
like influenza.

As hard as the fight against it may be, its mutations reveal that things can be 
a whole lot worse.

Of course, the coronavirus will continue to mutate as long as it still infects 
people. It’s possible that vaccines will have to change to keep up with the 
virus. And that’s why scientists need to keep tracking its history.

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