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Why the coronavirus affects children much less severely than adults has become an enduring mystery of the pandemic. The vast majority of children do not get sick; when they do, they usually bounce back.
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The first study that compared the immune response in children with that of adults suggests a reason for the relative good fortune of children. In children, a branch of the immune system that evolved to protect against unknown pathogens rapidly destroys the coronavirus before it causes damage to their bodies, according to the research published this week in Science Translational Medicine.
“The bottom line is that yes, children respond differently immunologically to this virus and it appears to protect children,” said Dr. Betsy Herold, a pediatric infectious disease expert at the Albert Einstein School of Medicine who led the study.
In adults, the immune response is much more attenuated, she and her colleagues found.
When the body encounters an unknown pathogen, it responds within hours with a burst of immune activity, called an innate immune response. The body’s defenders are quickly recruited for the fight and begin signaling for reinforcements.
Children more often encounter pathogens that are new to their immune systems. Her innate defense is swift and overwhelming.
Over time, as the immune system finds pathogen after pathogen, it builds up a repertoire of known villains. When the body reaches adulthood, it relies on a more sophisticated and specialized system adapted to remember and combat specific threats.
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If the innate immune system resembles the first responders on the scene, the adaptive system represents the trained specialists in the hospital.
The adaptive system makes sense biologically because adults rarely encounter a virus for the first time, said Dr. Michael Mina, a pediatric immunologist at the Harvard TH Chan School of Epidemiology in Boston.
But the coronavirus is new to everyone and the innate system fades as adults age, leaving them more vulnerable. In the time it takes for an adult body to put its specialized adaptive system into operation, the virus has had time to do damage, Herold’s research suggests.
She and her colleagues compared immune responses in 60 adults and 65 children and young adults under the age of 24, all of whom were hospitalized at Montefiore Medical Center in New York City from March 13 to May 17.
The patients included 20 children with multisystem inflammatory syndrome, the severe and sometimes fatal immune overreaction related to coronavirus.
In general, children were only mildly affected by the virus, compared to adults, and most reported gastrointestinal symptoms such as diarrhea and loss of taste or smell. Only five children required mechanical ventilation, compared with 22 of the adults; two children died, compared with 17 adults.
The children had much higher blood levels of two particular immune molecules, interleukin 17A and interferon gamma, the researchers found. The molecules were more abundant in younger patients and progressively decreased with age.
“We think you’re protecting these younger children, particularly from serious respiratory illnesses, because that’s really the main difference between adults and children,” Herold said.
In some adult Covid-19 patients, he added, the lack of a strong early response can also trigger an intense and unregulated adaptive reaction that can lead to acute respiratory distress syndrome and death.
All viruses have tricks to evade the innate immune system, and the coronavirus is particularly adept. Produced early in the course of infection, interleukin 17A can help children thwart the virus’s attempts to evade the innate response and protect itself from the later adaptive response.
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“We think that also protects them from generating a more vigorous adaptive immune response that is associated with that hyperinflammation,” Herold said.
Other experts said the study was well done, but suffered, as most coronavirus studies do, from enrolling patients too late in the infection.
The innate immune response is triggered hours after exposure to a pathogen, but people generally don’t arrive at the hospital until about a week after infection with the coronavirus, when symptoms are severe, said Akiko Iwasaki, an immunologist at the University of Yale.
It is too late to study how the innate immune system responds to the virus, he said, adding: “By the time people get sick, that time is over.”
Still, the new data negates a couple of popular theories about why children are protected from the virus, he said.
Some scientists have suspected that children may do better because they tend to have had more recent exposure to the coronaviruses that cause common colds, which could offer them some protection.
But the new study found no significant difference in immune responses to those viruses between the groups, Iwasaki noted.
Another theory held that children generate a stronger antibody response that clears the virus more efficiently than in adults. But the new study found that the sickest older people actually produced the most powerful antibodies.
That result may confirm a persistent concern among researchers – that the presence of these potent antibodies contributes to the disease in adults, rather than helping them fight the virus, a phenomenon called antibody-dependent enhancement. Vaccine manufacturers are carefully monitoring trial subjects for signs of this problem.
“That’s a topic that everyone has been dancing about,” said Dr. Jane C. Burns, an expert in pediatric infectious diseases at the University of California, San Diego. “Is it possible that high titers of some antibodies are actually bad for you, rather than good for you?”
Researchers also need to know what happens in children after the initial immune surge, Burns said. Children produce a strong immune response, but their bodies must turn it off quickly after the danger has passed.
If this virus becomes endemic, like the coronaviruses that cause common colds, children will eventually develop such strong adaptive defenses that they will not experience the problems adults are having now, Mina said.
“Over time, we will grow old from this virus.”
