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Scientists are Hunting for California’s Next COVID Variant

The state “has really increased the amount of COVID sequencing that is happening, but they’re doing it on this really broad scale, where they’re collecting big numbers so they can make big, broad statements about things.”

A computer graphic of the COVID-19 virus.
(TNS) - At the start of the year, infectious disease experts across California were, in their own words, stumbling around in a blind frenzy.

A new variant of the coronavirus was raging across the United Kingdom, causing unprecedented spikes in cases and deaths. California was similarly overwhelmed by a surge in winter cases — but here, very little high-tech testing was being done to identify the source of those infections. When California scientists finally discovered a locally bred variant, it was almost by accident. The mutant virus had long since gained a foothold and spread widely.

That experience raised alarms, statewide and nationally, and spurred fresh efforts and funding for genomic sequencing, the main tool scientists use to hunt for variants.

As a result, sequencing has exploded since January in California. It jumped sixfold in California in April alone, when nearly 20,000 genomic sequences from the state were deposited in a global database — more than from all but four countries. Across the U.S., sequencing increased more than fourfold in May from January.

California is now sequencing up to 10% of all coronavirus cases, a huge improvement from less than 0.5% at the start of the year. That means the state is now, finally, doing enough sequencing that infectious disease experts say they have a good grasp of the types of variants spreading here, and they are confident that scientists will be able to spot any new mutations quickly.

"We've got enough visibility to feel comfortable that we know which variants are emerging and how quickly they're moving and whether they're getting a foothold," said Dr. Sara Cody, the Santa Clara County health officer.

Sequencing began picking up nationwide in February, with $200 million from the Biden administration directed toward the federal Centers for Disease Control and Prevention. In April, the administration promised an additional $1.7 billion in coronavirus stimulus money for sequencing by the CDC and at the state level. That funding is meant to expand geographic coverage with sequencing and improve tracking and study of emerging variants.

There's certainly room for improvement in California, many infectious disease experts say. The state may have a great overview of the pandemic's genetic stamp, but most counties still don't have access to enough sequencing to understand what's happening in neighborhoods or to quickly identify and control local outbreaks.

Some scientists worry that the state is missing data within certain vulnerable communities, such as farmworkers or people without reliable access to health care. They also complain of a lack of cooperation between the public health gatekeepers of demographic data and the academic researchers who could use that information to paint a more nuanced portrait of where and how the virus is spreading.

The state "has really increased the amount of COVID sequencing that is happening, but they're doing it on this really broad scale, where they're collecting big numbers so they can make big, broad statements about things. It has increased, but I think that it's not the way that we need it to go forward," said Stacia Wyman, senior genomics scientist at the Innovative Genomics Institute at UC Berkeley. "We need to really, really stay on our toes about this."

Genomic sequencing provides the genetic blueprint of a virus — essentially, the instructions for its reproduction. Sequencing can reveal mutations to that genetic code. Those mutations, if they become permanent, can lead to new variants.

State and federal public health officials have identified about 10 variants in the U.S. that are cause for concern, because they may be more infectious, cause more serious illness or show signs of vaccine resistance. So far none of those variants is causing big problems in California and the vaccines are effective against all of them, but new variants are constantly emerging in other parts of the world.

In some ways, sequencing becomes even more important as California approaches the end of its pandemic, infectious disease experts said. It will be critical to study coronavirus illnesses in vaccinated people — known as breakthrough cases — to determine whether new variants are becoming resistant.

Sequencing also will help county health officials quickly identify local clusters of cases and stamp them out before they can trigger more widespread community transmission. For example, if two employees at the same grocery store test positive, health officials can use sequencing to determine if they are infected with the same variant — a sign that an outbreak is brewing and aggressive workplace safety measures need to be put in place.

"Expanded sequencing capacity in combination with other public health surveillance will be an important part of the pandemic end game," said Dr. Benjamin Pinsky, head of the Stanford Clinical Virology Laboratory.

Although the state still needs to ramp up local sequencing efforts, many experts said, California has made significant progress.

Once relegated to academic and high-end commercial laboratories, genomic sequencing is becoming more mainstream — a process sped up by the pandemic. Over the past six months alone, more than 14 California counties have started doing their own sequencing.

The equipment, roughly the size of a kitchen oven, now sits in labs as remote as Tulare and Humboldt counties. Five Bay Area counties have purchased sequencing equipment since the end of last year, and all of them have access to regional laboratories that can do sequencing for them. Genomic sequencing equipment varies dramatically in cost, but counties report spending about $150,000 on all the entry-level supplies.

"Genomic sequencing is a great tool in terms of understanding what we're seeing in our community. And having your own capacity in your own lab gives you faster turnaround time and better surveillance," said Dr. Sefanit Mekuria, deputy health officer for Contra Costa County.

Contra Costa's lab started its own sequencing in April and now does about 30 sequences a week. Mekuria said having in-house sequencing is most useful for providing results in days instead of weeks, as was the case when the county sent samples to other labs.

Building up a sequencing lab was no small task. Contra Costa had to buy equipment, figure out how to store large amounts of data associated with sequencing and train staff to analyze that data and apply it to case investigations. Before the pandemic, people who did sequencing typically had advanced degrees in bio-informatics — not a topic most county public health workers are deeply familiar with.

"There's a lot more that goes into it than just buying the sequencer," said Patrick Ayscue, an epidemiologist and senior fellow with the Chan Zuckerberg Biohub, a nonprofit in San Francisco's Mission Bay.

The Biohub provided sequencing for counties starting last summer, when public health officials had limited access to the technology. By the fall it was responsible for roughly half of all sequencing in California, and as of the end of May it had completed more than 12,000 sequences, Ayscue said.

But the Biohub has largely stopped doing that work for the state and counties as public health labs have stepped up.

"We're not disappearing. If stuff pops up and surge capacity is needed, we'll be around to help support if things fall through the floor," Ayscue said. "But I don't think anyone viewed it as desirable for this important public health function to be reliant on a nonprofit in the long term. And the state has gotten access to extensive sequencing capacity just within the last few months."

Since fall, scientists from the Biohub have helped Santa Clara County and about a dozen others in the state set up in-house sequencing operations, assisting them in choosing equipment and figuring out how to store data to analyzing complex genomic reports.

County health officials have used sequencing to get finely detailed information about how the virus is spreading in their communities. But sequencing will be useful after the pandemic, too, for everything from identifying drug-resistant sexually transmitted diseases to controlling valley fever, public health officials said.

"Sequencing has been a bucket list item to add to our repertoire for years. But it's always about money, funding. Even lab space for us is a big deal," said Jeremy Corrigan, manager of the Humboldt County public health laboratory. "We have been taking every opportunity we can to build our infrastructure and equipment and supplies using COVID funding opportunities. We want to be better prepared for the next pandemic."

Erin Allday is a San Francisco Chronicle staff writer. Email: eallday@sfchronicle.com Twitter: @erinallday

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