Scientists examine kids’ unique immune systems as more fall victim to Covid

Experts say it’s a question of basic math. “If 10 times as many kids are infected with Delta than previous variants, then, of course, we’re going to see 10 times as many kids hospitalized,” said Dr. Dimitri Christakis, director of the Center for Child Health, Behavior and Development at the Seattle Children’s Research Institute.

But the latest surge gives new urgency to a question that has mystified scientists throughout the pandemic: What protects most children from becoming seriously ill? And why does that protection sometimes fail?

“This is an urgent and complex question,” said Dr. Bill Kapogiannis, senior medical officer and infectious-disease expert at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“We are doing everything we can to address it, using all the tools we have available,” Kapogiannis said. “Answers can’t come soon enough.”

Investigating Immune Systems

For much of the pandemic, doctors could only guess why children’s immune systems were so much more successful at rebuffing the coronavirus.

Despite the alarming number of hospitalized children in the recent surge, young people are much less likely to become critically ill. Fewer than 1% of children diagnosed with covid are hospitalized and about 0.01% die — rates that haven’t changed in recent months, according to the American Academy of Pediatrics. Most children shrug off the virus with little more than a sniffle.

These membranes act like the layered stone walls that protected medieval cities from invaders. They’re made of epithelial cells — these also line many internal organs — which sit side by side with key soldiers in the immune system called dendritic cells and macrophages, said Betsy Herold, chief of the division of pediatric infectious diseases at the Albert Einstein College of Medicine.

Significantly, these cells are covered in proteins — called pattern recognition receptors — that act like sentries, continuously scanning the landscape for anything unusual. When the sentries notice something foreign — like a new virus — they alert cells to begin releasing proteins called interferons, which help coordinate the body’s immune response.

That allows kids to immediately activate their innate immune system, releasing interferons that help shut down the virus before it can establish a foothold, Eils said.

In comparison, adults have far fewer sentinels on the lookout and take about two days to respond to the virus, Eils said. By that time, the virus may have multiplied exponentially, and the battle becomes much more difficult.

When innate immunity fails to control a virus, the body can fall back on the adaptive immune system, a second line of defense that adapts to each unique threat. The adaptive system creates antibodies, for example, tailored to each virus or bacterium the body encounters.

While the adaptive immune system can be effective, it can sometimes cause more harm than good.

Like soldiers who kill their comrades with friendly fire, a hyperactive immune system can cause collateral damage, triggering an inflammatory cascade that tramples not just viruses, but also healthy cells throughout the body.

In some Covid patients, uncontrolled inflammation can lead to life-threatening blood clots and acute respiratory distress syndrome, which occurs when fluid builds up in the air sacs of the lung and makes it difficult to breathe, Betsy Herold said. Both are common causes of death in adult covid patients.

Because kids typically clear the coronavirus so quickly, they usually avoid this sort of dangerous inflammation, she said.

Kids are born with lots of these cells, but their numbers decline with age. And both children and adults who are sick with Covid tend to have fewer of these repair cells, Luban said.

Men also have fewer repair cells than women, which could help explain why males have a higher risk of dying from Covid than females.

Unanswered Questions

Scientists have fewer clues about what goes wrong in certain children with Covid, said Kevan Herold, who teaches immunobiology at the Yale School of Medicine.

Research suggests that children have more robust innate immune systems than adults because they have experienced so many recent respiratory infections, within their first few years, which may prime their immune systems for subsequent attacks.

But not all children shrug off Covid so easily, Eils said. Newborns haven’t been alive long enough to prime their immune systems for battle. Even toddlers may fail to mount a strong response, he said.

At Children’s Hospital New Orleans, half of Covid patients are under 4, said Dr. Mark Kline, a specialist in infectious diseases and physician-in-chief.

“We’ve had babies as young as 7 weeks, 9 weeks old in the ICU on ventilators,” Kline said. “We had a 3-month-old who required ECMO,” or extracorporeal membrane oxygenation, in which the patient is connected to a machine similar to the heart-lung bypass machine used in open-heart surgery.

Even previously healthy children sometimes die from respiratory infections, from Covid to influenza or respiratory syncytial virus.

One thing hospitalized kids have in common is that almost none are vaccinated, said Dr. Mary Taylor, chair of pediatrics at the University of Mississippi Medical Center.

“There’s really no way to know which child with Covid will get a cold and be just fine and which child will be critically ill,” Taylor said. “It’s just a very helpless sensation for families to feel like there is nothing they can do for their child.”

Scientists have had more success illuminating why certain adults succumb to covid.

Autoantibodies are very rare in children and young adults, however, and unlikely to explain why some youngsters succumb to the disease, said study co-author Dr. Isabelle Meyts, a pediatric immunologist at the Catholic University of Leuven in Belgium.

Two months into the delta surge, hospitals throughout the South are seeing a second wave of children with a rare but life-threatening condition called multisystem inflammatory syndrome, or MIS-C.

Although scientists still don’t know the exact cause of MIS-C, research by Yonker of Massachusetts General and others suggests that viral particles may leak from the gut into the bloodstream, causing a system reaction throughout the body.

“We certainly don’t know at this point whether children have more severe disease, but we’re keeping our eye on it,” he said.

To protect children, Fauci urged parents to vaccinate themselves and children age 12 and up. As for children too young for Covid shots, “the best way to keep them safe is to surround them by people who are vaccinated.”