Scientists at Children’s Hospital Los Angeles (CHLA) have been paying close attention to the behavior of SARS-CoV-2 since the beginning of the pandemic. This means reading out the genetic sequence of the virus from every COVID-19-positive sample to identify mutations. But this also means alerting authorities to notable changes in the virus.
Recently, their research uncovered mutations recognized by the global scientific community, mutations that may explain why certain versions of the virus—like the Delta variant—are so much more contagious.
“Genomic surveillance is critical,” says Xiaowu Gai, Ph.D., Director of Bioinformatics in the Center for Personalized Medicine at Children’s Hospital Los Angeles. “This is the only tool we have to identify mutations. We can track these mutations to help guide public health measures.”
Gai says sequencing the genome of SARS-CoV-2 allowed for development of the vaccine. “Now it remains just as important given the evolving virus and all its variants,” he says.
SARS-CoV-2 has infected more than 200 million individuals worldwide, giving it ample chance to mutate—and it continues to mutate every couple of weeks.
At CHLA, scientists in the Department of Pathology & Laboratory Medicine and the Center for Personalized Medicine have been tracking these mutations since the beginning of the pandemic to identify variants and anticipate the emergence of “variants of concern,” which can potentially be more contagious or cause more severe disease.
Sequencing critical to understanding variants
Understanding and awareness of variants depends on scientists tracking the mutations using sequencing technology. With specialized high-throughput machines, scientists can read the entire genetic sequence of SARS-CoV-2.
Then, samples can be compared to determine where mutations have arisen. This allows public health officials to be aware of the presence of different variants and the emergence of new more contagious strains of SARS-CoV-2.
At CHLA, Gai and his colleagues have sequenced every COVID-19-positive sample they have received since the beginning of the pandemic, over 3,000 samples to date. In addition to sequencing, Gai’s bioinformatics team analyzes the results for viral mutations.
This allows them to identify existing and emerging variants to support CHLA’s contact tracing and genomic epidemiology efforts to track transmission patterns. The team then shares findings with databases used to by investigators studying COVID-19 around the world.
Sharing information across the world
Working with Jennifer Dien Bard, Ph.D., and colleagues in the Department of Pathology & Laboratory Medicine, Gai and his team have helped CHLA publish the result of multiple SARS-CoV-2 studies, including the largest pediatric COVID-19 study of its time last year, which identified a potential link between certain mutations and severity of disease in children. Another publication demonstrated the effectiveness of public safety measures in limiting the spread of specific strains of the virus.
The team’s most recent work reveals mutations in genes that affect the virus’s ability to bind to and infect human cells. One study identified a sub-lineage of the Alpha variant that became officially recognized and named “Q.3.” in the internationally recognized SARS-CoV-2 classification system Pangolin.
One of the mutations they reported in the paper (called “M:I82T”) is now a recognized feature in the well-known Delta variant. “This mutation affects a protein that sits on the surface of the virus,” says Lishuang Shen, Ph.D., Senior Bioinformatics Scientist at CHLA and the first author of the publication. “This mutation may indeed be the reason the Delta variant is so much more infectious and—in some cases—more deadly.”
A second study identified the emergence of a mutation that increased in frequency by more than a factor of 10 in the United States in just two months (February through April of 2021). The team is carefully tracking the mutation for any signs that it may contribute to an emerging variant of concern.
“We need to know what is happening with this virus in as much detail as possible,” says Gai. “Sequencing COVID-19-positive samples allows us to do this.” Keeping tabs on the behavior of the virus will alert public health officials to things like how well the vaccine works against new variants.
The work continues
At the beginning of the pandemic, Gai and his colleagues in the Department of Pathology & Laboratory Medicine and Center for Personalized Medicine began working around the clock to keep up with testing and sequencing. Almost a year and a half into the pandemic, the team continues to remain vigilant. “The pandemic is not going away,” says Gai, “so neither are we.”
