The Science Behind Why Children Fare Better With Covid-19

By Sarah Toy

Children’s seeming imperviousness to Covid-19’s worst effects has been one of the biggest mysteries—and reliefs—of the pandemic. Now the reasons are coming into focus, scientists say: Children mobilize a first line of defense known as the innate immune system more effectively than adults.

Although some children do fall seriously ill after coming down with Covid-19, the most have mild symptoms or no symptoms at all. Unlike other respiratory viruses such as the flu or respiratory syncytial virus, SARS-CoV-2 doesn’t hit children nearly as hard as it does adults or the elderly.

The lower risk to children has discouraged some parents from getting them vaccinated. Vaccination rates among children eligible for Covid-19 shots lag far behind those for adults. Public-health experts say they want to explain the science behind children’s stronger protection against Covid-19 while still emphasizing that vaccines are important to protect vulnerable children and control infections. Covid-19 hospitalization rates for children reached records in January as the Omicron variant drove cases far past previous pandemic peaks.

“Some do get quite ill,” said Lee Beers, a professor of pediatrics at Children’s National Hospital in Washington.

The immune system consists of different lines of defense. Innate immunity coordinates the initial response against an infection, while adaptive immunity develops more slowly and mounts a more specific defense.

To understand why children fare better than adults against Covid-19, said Kevan Herold, a professor of immunobiology and internal medicine at Yale University, imagine the immune system as a medieval fortress. The innate response, which includes mucus in the nose and throat that helps trap harmful microbes, is like the moat, keeping assailants out. Innate immunity also includes proteins and cells that trigger the body’s initial immune response. Dr. Herold likens them to cannonballs launched as the enemy is beginning an invasion.

A second line of defense, the adaptive immune system, includes T cells and B cells. The adaptive immune system takes longer to initiate a response, but can remember specific weaknesses of past invaders. Think of them as soldiers preparing for battle inside the fortress, Dr. Herold said.

Innate immunity doesn’t have the same kind of memory. It relies on patterns associated with harmful microbes more generally. Immunologists have found that children’s immune systems have higher levels of some innate molecules and increased innate responses compared with adults. Experts including Dr. Herold and his wife, Betsy Herold, a pediatric infectious-disease doctor at the Children’s Hospital at Montefiore in the Bronx, think this is key to helping children better fight off the virus that causes Covid-19.

As Covid-19 swept across New York in early 2020, the Herolds set out to figure out why so many more adults were ending up in hospitals with Covid-19 than children. With other researchers, they initiated studies looking at children’s immune systems. They started with what Betsy Herold called the lowest-hanging fruit: cytokines, small proteins produced by a range of cells that help them communicate with each other.

Two cytokines important to the innate immune response are less prevalent in the blood of older people compared with younger people, they found. “That’s where the idea that it was an innate response started to be developed,” Betsy Herold said.

The Herolds’ study comparing 65 young patients and 60 adults with Covid-19 in New York City found that children were less reliant on the adaptive immune system than adults, likely because they had a stronger innate response.

They also looked at nose-and-throat swabs of 12 children and 27 adults and found that more genes involved in innate immunity were activated in the children, who also had higher levels of cytokines involved in innate immunity.

A lack of immune memory relative to adults may also give children an advantage in fighting off SARS-CoV-2, said Amy Chung, a researcher at the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia. After exposing the blood of healthy people to the pandemic coronavirus, she and her colleagues found that healthy seniors had strong pre-existing antibody responses to Covid-19, likely because they had been exposed many times to other coronaviruses, such as those that cause common colds.

Children, on the other hand, don’t have as strong of a pre-existing antibody response, said Dr. Chung, because they have had less exposure to other coronaviruses. While that might not seem like a good thing, in this case it confers an advantage: When children encounter SARS-CoV-2, they mobilize and attack the essential parts of the virus immediately.

Older people’s immune systems are targeting parts of the SARS-CoV-2 virus they have encountered in other coronaviruses. “Those parts don’t seem to be as important to stopping infection,” Dr. Chung said.

Children’s relative resilience to Covid-19 has led some parents to keep eligible children from getting vaccinated. The Kaiser Family Foundation’s most recent survey of 420 parents found that half weren’t too worried or not worried at all about their child getting seriously ill from Covid-19.

Kate Symonds said she doesn’t plan to get her 2-year-old and 9-month-old children vaccinated when they are eligible because of the relatively lower risk of severe illness and because she is worried about possible adverse effects from the shots.

“If it was a disease that was affecting young people more than older people, my opinions might be different, but that’s not the case,” said Ms. Symonds, 40, who lives in Canandaigua, N.Y. She said her husband is vaccinated and that she isn’t.

Vaccination rates among people under the age of 18 are significantly lower than those of adults, according to data from the Centers for Disease Control and Prevention. Around 40% of eligible children are fully vaccinated, compared with about three-quarters of eligible adults.

Researchers haven’t found evidence that Covid-19 vaccines pose any serious safety concerns. In trials conducted on thousands of children, the most common side effects of the vaccine were mild and didn’t have any lasting impact, the CDC said.

Covid-19 vaccines aren’t yet available for children under age 5. U.S. health regulators delayed their review of the Pfizer Inc. - BioNTech SE Covid-19 vaccine for that age range because the initial two-dose series wasn’t working well so far against the Omicron variant during testing.

Even if vaccines are available for this younger group, only 31% of parents of children that age say they would get their child vaccinated right away, according to the Kaiser poll. Around one-quarter of parents said they would definitely not get their child vaccinated.

But children’s risk of getting infected with Covid-19 appears similar to that of adults, recent research suggests, and children appear better at spreading the virus than early studies suggested.

Some children do require hospitalization with Covid-19 and some continue to have symptoms long after they have cleared the virus, said Betsy Herold. Children also are at risk for multisystem inflammatory syndrome, or MIS-C, a rare condition that can occur in children several weeks after Covid-19 infection. MIS-C can lead to organ damage or even death.

“The innate barrier is not 100% protective,” Betsy Herold said.

While that protection is robust, she said, Covid-19 still presents risks to children including the possibility of lingering symptoms. Without vaccination, she said, “you’re taking a gamble.”

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