CTSA Program Funding Laid Groundwork for Discovery of B.1.1.7 Variant in California

At 2:30 in the morning last December, researchers at a Scripps Research lab in La Jolla were fairly certain they had identified the first B.1.1.7 variant of SARS-CoV-2 in California. They had received a sample a few hours before that their collaborating institution, the University of California, San Diego (USCD), suspected could be it. After hours of sequencing, there were only a few more gaps in the genome to fill in.

Finally, at around 8 a.m. the next morning, researchers Dr. Mark Zeller and Karthik Gangavarapu from the Andersen Lab confirmed that it was, in fact, the variant. They immediately notified the lab’s principal investigator, Dr. Kristian Andersen, UCSD and the county.

“I think we expected to find the variant at some point, we just didn’t think it would be that early,” Gangavarapu said. “This was December 30.”

The B.1.1.7 variant, sometimes called the UK variant, was first detected in the U.S. just one day before, on December 29, in Colorado. It is considered a “Variant of Concern” by the CDC, and it has a higher rate of transmission than the wild SARS-CoV-2 strain. Its presence in the United States, is “concerning,” Gangavarapu said. “If not controlled properly, you would expect a surge in cases.”

The Andersen Lab’s discovery of the B.1.1.7 variant was made possible because of groundwork laid using funding from the Clinical & Translational Science Award (CTSA) Program from the National Center for Advancing Translational Sciences.

The Andersen Lab

Prior to the COVID-19 pandemic, researchers in Andersen Lab sequenced samples from other outbreaks, including Zika and Ebola. When the COVID-19 pandemic hit, the lab focused mostly on COVID testing, which was not yet widely available.

“It was a lot of improvisation in the beginning,” Zeller said. “There were shortages of everything.”

When COVID testing increased in San Diego, the lab migrated to sequencing positive samples. The researchers reached out to health departments and hospitals to find new COVID samples and older respiratory flu samples, where COVID cases may have been missed.

The beginning of the pandemic also happened to coincide with Scripps’ CTSA pilot funding award cycle, and Dr. Andersen received an award for San Diego Epidemiology and Research for COVID-19 Health (SEARCH). SEARCH is a collaboration across institutions to study COVID-19 in San Diego.

The lab began working with SEARCH partners Rady Children’s Hospital and University of California, San Diego, which were screening local physicians to see how many healthcare workers were affected early in the pandemic.

“The pilot [funding] allowed the Andersen  Lab to sequence positive samples from that cohort, which let them have some money to develop the workflows and the collaborations, which led to further funding through the CDC,” said Dr. Emily Spencer, the associate director at Scripps Research Translational Institute.

The Andersen Lab received a $2.5 million grant from the CDC to continue this work, which Zeller estimates the lab has been using for about the past year. The funding allowed them to ramp up the number of genomes they sequenced and form new collaborations. Now the lab sequences a couple hundred genomes per week, getting samples from the county and UCSD.

The lab also receives other limited information about the sample, including the sample collection date and the ZIP code. The researchers are working on an in-depth analysis of the COVID spread across San Diego using that information, but Gangavarapu said this process will take longer.

“That’s not a process that we do in real time,” he said. “In real time, what we do track is, for example, what is the prevalence of a certain mutation? And is there some new mutation that arose that we need to take a look at?”

Sharing Data

In addition to sequencing genomes, the Andersen Lab also helped create Outbreak.info, a National Center for Data to Health (CD2H) project and database of open-source SARS-CoV-2 data and resources from across the world. Researchers can use the database to track how COVID-19 cases and deaths change over time and in different locations

“I think open data is absolutely essential, especially in a pandemic situation like this,” Gangavarapu said. When the Andersen Lab first sequenced B.1.1.7, the researchers immediately made the sequence available online. In partnership with another organization, Helix, which also released its data, the Andersen Lab was able to put together a bigger study about B.1.1.7 across the United States.

“None of that would have been possible without us sharing, them sharing and the sharing of open data,” Gangavarapu said, adding that data quality increases when data is open sourced, because other researchers can look at it and check for errors. The Andersen Lab also shares sequencing protocols and computational tools used to process the data.

As the vaccination process progresses in the United States, and immunity generally increases, Gangavarapu said it’s even more important to keep track of which variants are arising and to be on the lookout for the ones that could evade immune responses.

“We’re sequencing a random set of samples to keep track of how the different variants are spreading over time,” he said. “The B.1.1.7 variant is a classic example of why that surveillance is important.”