USA TODAY US Edition

Scientists hunt down 8 strains of the virus

No variation found to be more deadly than others

- Elizabeth Weise SCRIPPS RESEARCH

SAN FRANCISCO – At least eight strains of the coronaviru­s are making their way around the globe, creating a trail of death and disease that scientists track by their genetic footprints.

Though much is unknown, hidden in the virus’ unique microscopi­c fragments are clues to its original strain, how it behaves as it mutates and which strains turn into conflagrat­ions while others die out thanks to quarantine measures.

Researcher­s are focused on tracking the strains of the SARS-CoV-2 virus that cause the illness COVID-19.

Labs around the world turn their machines to the task of rapidly sequencing the genomes of virus samples taken from people sick with COVID-19. The informatio­n is uploaded to a website called NextStrain.org that shows how the virus migrates and splits into similar but new subtypes.

Though researcher­s cautioned they see only the tip of the iceberg, the tiny difference­s between the virus strains suggest shelter-in-place orders work in some areas and no one strain of the virus is more deadly than another. They said it does not appear the strains will grow more lethal as they evolve.

“The virus mutates so slowly that the virus strains are fundamenta­lly very similar to each other,” said Charles Chiu, a professor of medicine and infectious disease at the University of California­San

“The virus mutates so slowly that the virus strains are fundamenta­lly very similar to each other.” Charles Chiu Professor of medicine and infectious disease at the University of California, San Francisco School of Medicine

Francisco School of Medicine.

The SARS-CoV-2 virus began causing illness in China between mid-November and mid-December. Its genome is made up of about 30,000 base pairs. Humans, by comparison, have more than 3 billion. Even in the virus’ most divergent strains, scientists have found only 11 base pair changes. That makes it easy to spot new lineages as they evolve, Chiu said.

“The outbreaks are trackable. We have the ability to do genomic sequencing almost in real-time to see what strains or lineages are circulatin­g,” he said.

Most cases on the U.S. West Coast are linked to a strain first identified in Washington state. It may have come from a man who had been in Wuhan, China, the virus’ epicenter, and returned home Jan. 15. It is only three mutations away from the original Wuhan strain, according to work done early in the outbreak by Trevor Bedford, a computatio­nal biologist at Fred Hutch, a medical research center in Seattle.

On the East Coast, there are several strains, including the one from Washington and others that appear to have made their way from China to Europe, then to New York and beyond, Chiu said.

This isn’t the first time scientists have scrambled to do genetic analysis of a virus in the midst of an epidemic. They did it with Ebola, Zika and West Nile, but nobody outside the scientific community paid much attention.

“This is the first time phylogenet­ic trees have been all over Twitter,” said Kristian Andersen, a professor at Scripps Research, a nonprofit biomedical science research facility in La Jolla, California, speaking of the diagrams that show the evolutiona­ry relationsh­ips between different strains of an organism.

The maps are available on NextStrain, an online resource for scientists that uses data from academic, independen­t and government laboratori­es all over the world to visually track the genomics of the SARSCoV-2 virus. It represents genetic sequences of strains from 36 countries on six continents.

The maps can be a “little dangerous,” Andersen said. The trees showing the evolution of the virus are complex, and it’s difficult even for experts to draw conclusion­s from them. “Remember, we’re seeing a very small glimpse into the much larger pandemic. We have half a million described cases right now but maybe 1,000 genomes sequenced. So there are a lot of lineages we’re missing,” he said.

COVID-19 hits people differentl­y: Some feel slightly under the weather for a day, others are flat-on-theirbacks sick for two weeks and about 15% are hospitaliz­ed. About 1% of those infected die. The rate varies greatly by country, and experts said it is probably tied to testing rates rather than actual mortality.

Chiu said it’s unlikely the difference­s are related to people infected with different strains of the virus.

The COVID-19 virus does not mutate very fast. It does so eight to 10 times more slowly than the influenza virus, Andersen said, making its evolution rate similar to other coronaviru­ses such as Severe Acute Respirator­y Syndrome (SARS) and Middle East Respirator­y Syndrome (MERS). It’s not likely to spontaneou­sly evolve into a form more deadly to humans. The SARS-CoV-2 is so good at transmitti­ng itself between human hosts, Andersen said, it is under no evolutiona­ry pressure to evolve.

Shelter in place working in California

Chiu’s analysis shows California’s strict shelter in place efforts appear to be working.

More than half of the 50 SARS-CoV-2 virus genomes his San Francisco-based lab sequenced in the past two weeks are associated with travel from outside the state. Thirty percent are associated with health care workers and families of people who have the virus. “Only 20% are coming from within the community. It’s not circulatin­g widely,” he said.

The findings indicate the virus has not been able to gain a serious foothold because of social distancing, he said. It’s like a wildfire, Chiu said. A few sparks might fly off and land in the grass and start new fires. But if the main fire is doused and its embers stomped out, you can kill off an entire strain. In California, Chiu sees a lot of sparks hitting the ground, most coming from Washington, but they’re quickly being put out.

An example was a small cluster of cases in Solano County, northeast of San Francisco. Chiu’s team did a genetic analysis of the virus that infected patients there and found it was most closely related to a strain from China. At the same time, his lab was sequencing cases in Santa Clara. They discovered the patients had the same strain as those in Solano County. Chiu said someone in that cluster had contact with a traveler who returned from Asia. “This is probably an example of a spark that began in Santa Clara, may have gone to Solano County, but then was halted,” he said.

The virus, he said, can be stopped.

China is an unknown

Researcher­s don’t have a lot of informatio­n about the genomics of the virus inside China.

The virus’ initial sequence was published Jan. 10 by professor Yong-Zhen Zhang at the Shanghai Public Health Clinical Center. Chiu said scientists don’t know whether there was just one strain circulatin­g in China or more. “It may be that they haven’t sequenced many cases, or it may be for political reasons, they haven’t been made available,” Chiu said. “It’s difficult to interpret the data because we’re missing all these early strains.”

Researcher­s in the United Kingdom who sequenced the genomes of viruses found in travelers from Guangdong in south China found those patients’ strains spanned the gamut of strains circulatin­g worldwide. “That could mean several of the strains we’re seeing outside of China first evolved there from the original strain, or that there are multiple lines of infection. It’s very hard to know,” Chiu said.

The virus did not come from a lab

Though there remain many questions about the trajectory of the COVID-19 disease outbreak, one thing is broadly accepted in the scientific community: The virus was not created in a lab but naturally evolved in an animal host.

SARS-CoV-2’s genomic molecular structure – think the backbone of the virus – is closest to a coronaviru­s found in bats. Parts of its structure resemble a virus found in scaly anteaters, according to a paper published this month in the journal Nature Medicine.

Someone manufactur­ing a virus targeting people would have started with one that attacked humans, National Institutes of Health Director Francis Collins wrote in an editorial that accompanie­d the paper.

 ?? SUSAN MERRELL/UCSF ?? Charles Chiu, a professor of medicine and infectious disease at the University of California, San Francisco School of Medicine, inserts a tray of vials into a Biomatrix sorter to study the genes of the coronaviru­s.
SUSAN MERRELL/UCSF Charles Chiu, a professor of medicine and infectious disease at the University of California, San Francisco School of Medicine, inserts a tray of vials into a Biomatrix sorter to study the genes of the coronaviru­s.
 ??  ?? Sharada Saraf prepares samples for testing in La Jolla, Calif.
Sharada Saraf prepares samples for testing in La Jolla, Calif.

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