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ANGELS–(COMMERCIAL THREAD) – The COVID-19 pandemic has introduced many new words into our daily lives. Beyond N95 and quarantine, new terms like Delta variant are now commonplace. But what is a variant? How are the variants identified? And why is it important to follow them?
Scientists at the Children’s Hospital of Los Angeles have been paying close attention to 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 it also means alerting authorities to notable changes in the virus. Recently, in fact, their research has uncovered mutations recognized by the global scientific community, mutations that may explain why certain versions of the virus, such as Delta variant-are so much more contagious.
“Genomic monitoring is essential,” says Xiaowu Gai, PhD, director of bioinformatics at the Center for Personalized Medicine at Children’s Hospital in Los Angeles. “This is the only tool we have to identify mutations. We can track these changes to help guide public health action. This follow-up has been essential throughout the pandemic.
“The sequencing of the SARS-CoV-2 genome enabled the development of the vaccine,” adds Dr. Gai. “Now that remains just as important given the evolution of the virus and all of its variants.”
What is a variant?
When a virus infects someone, it replicates, making many copies of itself. Inevitably, mistakes called mutations are made during this process. Sometimes these mutations facilitate the spread of the virus or the infection of cells. When this happens, the new version of the virus — or variant– will become more frequent in the population. The more a virus spreads from person to person, the more likely it is to mutate and develop new variants.
SARS-CoV-2 has infected more than 200 million people worldwide, giving it a high chance of mutating. Experts say SARS-CoV-2, the virus that causes COVID-19, mutates every two weeks. At the Los Angeles Children’s Hospital, scientists from the Department of Pathology and Laboratory Medicine and the Center for Personalized Medicine have been tracking these mutations since the start of the pandemic to identify variants and anticipate the emergence of “Variants of concern”, which can potentially be more contagious or cause more serious illness.
A family tree of viruses
Over time, a variant will develop its own mutations, leading to multiple sublines, much like a family tree. But not all mutations are cause for concern. In fact, many of them are irrelevant, just as removing a letter from a word always leaves a sentence that can be read. In some cases, mutations can even cause the virus to weaken and die. But in others, like the current Delta variant– these changes can promote the spread of a virus.
The Centers for Disease Control and Prevention (CDC) reports that the Delta variant is twice as contagious as the previous strains. This means that people exposed to the Delta variant are more likely to be infected and that over time, Delta variant surpasses other variants to become dominant. Today, more than 90% of new cases of COVID-19 are caused by the Delta variant.
Our understanding and knowledge of variants depends on scientists tracking mutations using a technology called sequencing. With specialized high-throughput machines, scientists can read the entire genetic sequence, sometimes called the genome, SARS-CoV-2. Then the samples can be compared to determine where the mutations appeared. 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.
Track the virus
At Los Angeles Children’s Hospital, geneticist Dr Gai and his colleagues have sequenced every COVID-19 positive sample they have received since the start of the pandemic, more than 3,000 samples to date. In addition to sequencing, Dr. Gai’s bioinformatics team analyzes the results of viral mutations. This allows them to identify existing and emerging variants to support CHLA’s contact tracing and genomic epidemiology efforts to track patterns of transmission. The team then shares the results with databases used by investigators studying COVID-19 around the world.
Sharing information around the world
Together with Jennifer Dien Bard, PhD, and colleagues in the Department of Pathology and Laboratory Medicine, Dr Gai and his team helped the CHLA publish the results of several SARS-CoV-2 studies, including its largest pediatric COVID-19 study last year, which identified a potential link between certain mutations and the severity of illness in children. Another publication has demonstrated the effectiveness of public safety measures in limiting the spread of specific strains of the virus.
As the pandemic reaches the milestone of a year and a half, Dr. Gai’s team is not slowing down. In fact, their recent work has 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 Alpha variant, which appeared in the UK in September 2020. The Alpha variant quickly became dominant, accounting for over 90% of cases in Europe and almost 60% of COVID-19 cases in the US, until the emergence of the Delta variant.
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 subline of Alpha variant which became officially recognized and named “Q.3”. in the internationally recognized classification system SARS-CoV-2 Pangolin. The study was also included in the CDC’s weekly Genomics and Public Health Precision Update on Genomics and Precision and cited by the Global Virus Network, an international resource portal for tracking mutations in the SARS-CoV-2.
One of the mutations they reported in the article (called “M: I82T”) is now a recognized feature in the well-known Delta variant. “This mutation affects a protein that is on the surface of the virus,” says Lishuang Shen, PhD, senior bioinformatics scientist at Los Angeles Children’s Hospital and first author of the publication. “This mutation may indeed be the reason that 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 to April 2021). The team is closely monitoring the mutation for any signs that it may be contributing to an emerging variant of concern.
“We need to know what’s going on with this virus in as much detail as possible,” says Dr Gai. “Sequencing COVID-19 positive samples allows us to do this. Keeping an eye on the behavior of the virus will alert public health officials to things like the vaccine’s effectiveness against the new variants.
At the onset of the pandemic, Dr Gai and his colleagues in the Department of Pathology and Laboratory Medicine and the Center for Personalized Medicine began working around the clock to track testing and sequencing. Almost a year and a half after the start of the pandemic, the team continues to remain vigilant. “The pandemic is not going to go away,” says Dr Gai, “neither will we. ”
The team carrying out this work in the Department of Pathology and Laboratory Medicine and the Center for Personalized Medicine includes: Lishuang Shen, first author of the two new publications; Jennifer Dien Bard, PhD, director of clinical microbiology and virology laboratories; Maurice O’Gorman, PhD, Chief of Laboratory Medicine, Jaclyn Biegel, PhD, Chief of Genomic Medicine 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 Director General of the Center for Personalized Medicine.
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