Largest Genetic Study on Children with COVID-19 Takes a Closer Look at Mutations

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

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

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

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

An Ever-Changing Virus

Mutations are mistakes that occur in the virus’ genome—or genetic material—when it replicates. Most viruses experience some variation as they circulate a population. In SARS-CoV-2, many of the mutations are insignificant or may even weaken the virus. Others, however, may affect how easily the virus is transmitted and even how severe the illness is.

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

One common mutation, called D614G, causes changes in the spike protein of the virus. Though it was not prevalent when the virus began spreading worldwide earlier this year, the version has since become dominant worldwide. 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 gain entry to human cells, allows the virus to transmit more easily. There is not yet any conclusive evidence that this mutation changes the severity of disease symptoms.

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

Implications of Mutations

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

This relatively slow mutation rate can be helpful for scientists trying to get a handle on the novel virus. However, Ray cautions that as the population of infected people increases, so will the speed at which mutations happen.

With the introduction of solutions to support the immune system against the viral infection—such as vaccination, prior exposure to the virus, convalescent plasma, and antibody therapy—SARS-CoV-2 may evolve to evade immune responses. This means it’s possible that vaccine candidates that are currently promising may 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 accumulate and just the right ones could happen that could evade immune responses,” Ray says, who is not affiliated with the study.

Vaccines that have proven effective will still likely protect the body against the virus. But, as is true with other widespread viruses like influenza, supplemental or new versions of the vaccine may be needed to cover any new strains of the virus that emerge in the future.

Dealing With Unknown Variables

Though COVID-19 is often reported to be less severe for children than adults, one in three children hospitalized for the disease is admitted to the ICU, according to the study. Gai says that for those patients who experience a severe course of the disease, understanding the virus’s genetic composition could provide some key insight for treatment development.  

Still, the makeup of the virus itself can only tell geneticists so much about how it will impact people who are infected. They must also consider the demographics and genetic information of the infected person.

Gai cautions that while these findings may hint at a correlation between certain mutations and their outcomes, many larger studies are still required to show that a mutation definitely causes more severe illness. Despite being the largest genomic pediatric COVID-19 survey to date, it only included 141 children.

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

Additionally, the study did not account for differences in age, gender, pre-existing conditions, and other important factors. Findings related to the viral load of patients may also be skewed based on when samples were collected from the patients. Still, the study contributes to a growing body of knowledge on how genetic variation can shape important health outcomes.

“We need reports like this to get a sense of how the virus is evolving,” Ray says. “Sequences from studies like this, when put together with sequences from all over the world, have a major value in helping us understand how this virus evolves and whether we need to adjust our strategies to manage it.”

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