Largest genetic study in children with COVID-19 takes a closer look at mutations

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Key points to remember

  • The Los Angeles Children’s Hospital has conducted the largest pediatric COVID-19 genomic investigation to date.
  • The study reports a possible link between certain mutations in SARS-CoV-2 and the severity of the disease.
  • The samples showed high levels of genetic variation in California.

Like many viruses, SARS-CoV-2, the virus that causes COVID-19, undergoes many genetic mutations as it spreads through a large population. Scientists are only beginning to understand these variations and their impact on health, especially in children.

In the largest pediatric COVID-19 genomic study to date, a team from Children’s Hospital in Los Angeles has found a link between viral mutations and disease severity. The November study was published in the journal Open Forum on Infectious Diseases.

“If we can do something to find out if there is a correlation between the genetics of the viral genome mutation and the disease phenotype (the observable characteristics of COVID-19), you can be told how best to treat the patient, “Xiaowu Gai, PhD, one of the study’s authors and director of bioinformatics at the Los Angeles Children’s Hospital, tells Verywell.

In an effort to better understand how genetic variation might affect a pediatric population, the research team analyzed genetic information for the virus from 141 children infected between March 13 and June 16. These samples showed a high level of variation and the prevalence of a common mutation associated with higher transmission rates.

What it means for you

The genetic material of SARS-CoV-2, the virus that causes COVID-19, is continually evolving. Scientists are working to understand how genetic mutations can affect the transmission of the virus and the severity of the disease in infected patients.

A constantly evolving virus

Mutations are errors that occur in the genome or genetic material of the virus when it replicates. Most viruses undergo variations as they circulate in a population. In SARS-CoV-2, many mutations are insignificant or can even weaken the virus. Others, however, can affect the ease of transmission of the virus and even the severity of the disease.

“When a lot of people think of COVID-19, they think of this one thing, this oddity,” Gai says. “But that’s not the way we see it. The virus in the body of any patient with a viral infection is a mixture of many different copies of this virus.

A common mutation, called D614G, causes changes in the virus spike protein.Although it was not widespread when the virus began to spread around the world earlier this year, the version has since become dominant around the world. The authors report that it was present in 99.3% of the pediatric samples they collected.

The D614G mutation, which increases the spike protein used by the virus to enter human cells, allows the virus to be transmitted more easily. There is not yet conclusive evidence that this mutation changes the severity of the symptoms of the disease.

The COVID-19 spike protein mediates entry of the coronavirus into the host cell.??

The research team, however, found a link between the 20C clade – a mutated version of the virus – and more severe symptoms. The 20A, 20B and 20C clades are all recently mutated versions of the virus. All but one of the severe pediatric and moderately severe cases in this study carried a 20C version of the virus.

Implications of mutations

“When the public looks at a statement like this, it looks scary that the virus is mutating,” Stuart Campbell Ray, MD, infectious disease expert and professor of medicine at Johns Hopkins University told Verywell. “But all RNA viruses have a mutation rate. And the mutation rate of SARS-CoV-2 is about five times slower than that of the flu, at least it has been to date. ”

This relatively slow rate of mutation may be useful for scientists trying to bring the new virus under control. However, Ray warns that as the population of those infected grows, the rate at which mutations occur will also increase.

With the introduction of solutions to support the immune system against viral infection, such as vaccination, prior exposure to the virus, convalescent plasma, and antibody therapy, SARS-CoV-2 may evolve to escape the immune responses. This means that it is possible that vaccine candidates that are currently promising will become less effective in the coming months as the virus continues to mutate.

“There is a risk – because this pandemic is out of control – that these mutations could build up and the right mutations could occur that could elude immune responses,” said Ray, who is not affiliated with study.

Vaccines that have been shown to be effective will likely still protect the body against the virus. But, as is the case with other widespread viruses like influenza, additional or new versions of the vaccine may be needed to cover any new strain of the virus that emerges in the future.

Manage unknown variables

Although COVID-19 is often reported to be less severe in children than in adults, one in three children hospitalized with the disease is admitted to intensive care, according to the study.Gai says that for patients with severe disease progression, understanding the genetic makeup of the virus could provide key information for developing treatment.

Yet the makeup of the virus itself cannot tell the same to geneticists about its impact on those infected. They must also take into account the demographic and genetic data of the infected person.

Gai warns that while these findings may suggest a correlation between certain mutations and their results, many larger studies are still needed to show that a mutation definitely causes more serious disease. Although this is the largest pediatric COVID-19 genomic investigation to date, it only included 141 children.

“It’s not really a very large sample,” Gai says. “We cannot do the correlation analysis for each individual mutation with a disease phenotype.”

In addition, the study did not take into account differences in age, sex, pre-existing conditions and other important factors. Patient viral load results may also be skewed depending on when samples were collected from patients. Still, the study contributes to a growing body of knowledge about how genetic variation can shape important health outcomes.

“We need reports like this to get a sense of how the virus is progressing,” Ray said. “Study sequences like this, when combined with sequences from around the world, are of major value in helping us understand how this virus evolves and whether we need to adjust our strategies to deal with it.”

The information in this article is current as of the date shown, which means more recent information may be available as you read this. For the most recent updates on COVID-19, visit our coronavirus news page.


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