Scientists at Children’s Hospital Los Angeles have been paying close attention to the behavior of SARS-CoV-2 since the beginning of the pandemic. According to experts, SARS-CoV-2, the virus that causes COVID-19, mutates every couple of weeks. Their researchers reported in a blog on how they read the genetic sequence of the virus from every COVID-19-positive sample to identify mutations.
At Children’s Hospital Los Angeles, 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 in order to identify variants and anticipate the emergence of “variants of concern,” which can potentially be more contagious or cause more severe disease.
“Genomic surveillance is critical,” says Xiaowu Gai, PhD, 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.” This tracking has been critical throughout the pandemic. “Sequencing the genome of SARS-CoV-2 allowed for development of the vaccine,” adds Dr. Gai. “Now it remains just as important given the evolving virus and all its variants.”
Over time, a variant will develop new mutations of its own, leading to multiple sub-lineages, much like a family tree. But not all mutations are cause for concern. In fact, many of them are inconsequential, much like how dropping one letter from a word still leaves a sentence that can be read. In some cases, mutations may even cause the virus to become weaker and die off. But in others—such as the current Delta variant—these changes can help a virus spread.
Our understanding and awareness of variants depends on scientists tracking the mutations using a technology called sequencing. With specialized high-throughput machines, scientists can read the entire genetic sequence, sometimes called the genome, 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.
Dr. 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, Dr. 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.
Working with Jennifer Dien Bard, PhD, and colleagues in the Department of Pathology & Laboratory Medicine, Dr. 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. The study was also included in the CDC’s COVID-19 Genomics and Precision Public Health Weekly Update and cited by the Global Virus Network, an international resource portal for tracking SARS-CoV-2 mutations.
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, PhD, Senior Bioinformatics Scientist at Children’s Hospital Los Angeles 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.