A Pediatric Research Institution is Setting the Pace for Monitoring SARS-CoV-2 Mutations and COVID-19 Variants

LOS ANGELES–(BUSINESS WIRE)–The COVID-19 pandemic has introduced many new words into our daily lives. In addition to N-95 and quarantine, new terms like Delta variant are now commonplace. But what is a variant? How are variants identified? And why is it important to follow them?

Scientists at Children’s Hospital Los Angeles have been keeping a close eye on the behavior of SARS-CoV-2 since the start of the pandemic. This means reading the genetic sequence of the virus from each COVID-19 positive sample to identify mutations. But this also means warning authorities about notable changes to the virus. Recently, their research has even revealed mutations recognized by the global scientific community, mutations that may explain why certain versions of the virus, such as the Delta variant, are so much more contagious.

“Genomic surveillance is critical,” said 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 action.” This tracking has been critical during the pandemic.

“By sequencing the genome of SARS-CoV-2, the vaccine could be developed,” adds Dr. Go for it. “Now it remains just as important given the evolving virus and all its variants.”

What is a variant?

When a virus infects someone, it replicates and makes many copies of itself. In that process, inevitably mistakes are made called mutations. Sometimes these mutations make it easier for the virus to spread or infect cells. When this happens, the new version of the virus – or variant – will become more common in the population. The more a virus spreads from person to person, the more likely it has to mutate and develop new variants.

SARS-CoV-2 has infected more than 200 million individuals worldwide, giving it ample opportunity to mutate. According to experts, SARS-CoV-2, the virus that causes COVID-19, mutates every few weeks. At Children’s Hospital Los Angeles, scientists from the Department of Pathology & Laboratory Medicine and the Center for Personalized Medicine have been monitoring these mutations since the start of the pandemic to identify variants and anticipate the emergence of “variants of concern,” which could potentially be more contagious or cause a more serious illness.

A virus family tree

Over time, a variant will develop new mutations of its own, leading to multiple sublines, much like a family tree. But not all mutations are cause for concern. In fact, many of them are inconsistent, much like how dropping a letter from a word still leaves a sentence that can be read. In some cases, mutations can even cause the virus to weaken and die. But in others, such as the current Delta variant, these changes can help spread a virus.

The Centers for Disease Control and Prevention (CDC) reports that the Delta variant is twice as contagious as previous strains. This means that people exposed to the Delta variant are more likely to become infected, and over time the Delta variant competes with other variants to become dominant. Today, more than 90% of new COVID-19 cases are caused by the Delta variant.

Our understanding and awareness of variants depends on scientists tracking the mutations using a technology called sequencing. Specialized high-throughput machines allow scientists to read the entire genetic sequence, known as the genome, of SARS-CoV-2. Samples can then be compared to determine where mutations have occurred. 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.

Follow the virus

At Children’s Hospital Los Angeles, geneticist Dr. Gai and his colleagues sequenced every COVID-19-positive sample they’ve received since the start of the pandemic, more than 3,000 samples to date. In addition to sequencing, Dr. Gai the results on viral mutations. This allows them to identify existing and emerging variants to support CHLA’s contact tracing and genomic epidemiological efforts to monitor transmission patterns. The team then shares findings with databases used by researchers studying COVID-19 around the world.

Sharing information around the world

In collaboration with Jennifer Dien Bard, PhD, and colleagues from the Department of Pathology and Laboratory Medicine, Dr. Gai and his team helped CHLA publish the results of multiple SARS-CoV-2 studies, including the largest pediatric COVID-19 study of its time last year, which identified a possible link between certain mutations and the severity of the disease. disease in children. Another publication demonstrated the effectiveness of public safety measures in limiting the spread of specific strains of virus.

With the pandemic approaching a year and a half, Dr. Don’t go. Their recent work has even been recognized internationally.

Recently, researchers at the Center for Personalized Medicine analyzed more than 1.3 million SARS-CoV-2 genome sequences from global databases to trace the lineage of the Alpha variant, which surfaced in the UK in September 2020. The Alpha variant quickly became dominant, accounting for over 90% of cases in Europe and nearly 60% of COVID-19 cases in the United States, until the emergence of the Delta variant.

The team’s most recent work reveals mutations in genes that affect the virus’ ability to bind to and infect human cells. One study identified a sub-lineage of the Alpha variant that was 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 (named “M:I82T”) is now a recognized trait in the familiar Delta variant. “This mutation affects a protein that sits on the surface of the virus,” said Lishuang Shen, PhD, Senior Bioinformatics Scientist at Children’s Hospital Los Angeles and the lead author of the publication. “Indeed, this mutation may be the reason that the Delta variant is so much more contagious and — in some cases — more deadly.”

A second study identified the emergence of a mutation that increased in frequency by more than 10-fold in the United States in just two months (February to April 2021). The team is closely monitoring the mutation for signs that it may contribute to an emerging variant of concern.

“We need to know as much detail as possible about what’s happening with this virus,” said Dr. Gai. “By sequencing COVID-19-positive samples, we can do this.” By monitoring the behavior of the virus, public health officials are alerted to things like how well the vaccine works against new variants.

At the start of the pandemic, Dr. Gai and his colleagues from the Department of Pathology & Laboratory Medicine and the Center for Personalized Medicine work around the clock to track testing and sequencing. Almost a year and a half after the pandemic, the team remains vigilant. “The pandemic isn’t going away,” Dr. Gai says, “so neither are we.”

The team conducting this work in the Department of Pathology & Laboratory Medicine and the Center for Personalized Medicine includes: Lishuang Shen, lead author of both new publications; Jennifer Dien Bard, PhD, the director of the clinical microbiology and virology labs; Maurice O’Gorman, PhD, chief of laboratory medicine, Jaclyn Biegel, PhD, chief of genomics and director of the Center for Personalized Medicine, Timothy Triche, MD, PhD, co-director of the Center for Personalized Medicine; Alexander Judkins, MD, chief pathologist and executive director of the Center for Personalized Medicine.

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