COVID-19 is much less severe in children, and it could have to do with a child’s still-developing immune system.
By Sarah Zhang May 15, 2020
Only after New York City passed its current coronavirus peak did pediatricians notice a striking, new pattern: Dozens of kids who had been exposed to COVID-19 were coming in sick, but they weren’t coughing. They didn’t have severe respiratory distress. Instead, they had sky-high inflammation and some combination of fever, rashes on their hands and feet, diarrhea, vomiting, and very low blood pressure. When ICU doctors around the world gathered for a weekly online COVID-19 call on May 2, doctors elsewhere began sharing similar observations. “The tenor of the meeting completely changed,” says Steven Kernie, the chief of critical-care medicine at New York-Presbyterian Morgan Stanley Children’s Hospital, who was on the call.
Until then, the news about children and COVID-19, the disease caused by the novel coronavirus, had been largely good: Kids can get seriously sick, but they rarely do. They can spread the disease, but they do it less than adults. Study after study–in China, Iceland, Australia, Italy, and the Netherlands–has found children get less sick and are less contagious.
But a very small number of children seem to have a delayed reaction to the novel coronavirus–one that takes many weeks to manifest. What pediatricians first saw in Europe and New York is now named “pediatric multi-system inflammatory syndrome” (PMIS) or, per the Centers for Disease Control and Prevention, “multisystem inflammatory syndrome in children.” Since the New York City Health Department issues an alert on May 4, 82 such cases have been confirmed in the city. Most patients have recovered or are recovering, but one child has died. Across the country, doctors are finding similar cases. PMIS does seem to be a phenomenon unique to kids.
But the virus is the same, whether it infects adult or child. The question is, why does COVID-19 affect them so differently? Both striking patterns in kids–the fact that most do not get very sick but a small number still end up with a delayed inflammation syndrome–may be rooted in a child’s still-developing system. And although COVID-19 is a new disease, these patterns are seen with other viruses too.
Immune systems change with age, becoming weaker or stronger in different ways. An adult’s body might be better armed against familiar threats, but more inflexible against novel ones. The two human viruses most closely related to the coronavirus that causes COVID-19 are the ones behind SARS and MERS–both also coronaviruses, a large family that infects many animal species. SARS likely jumped from bats to civet cats to humans in 2002, and MERS from camels to humans in 2012. Both have a much higher fatality rate than COVID-19 and neither exploded into a pandemic on the current scale, giving us smaller numbers from which to draw conclusions. Still, they too seemed to have largely spared children.
Like COVID-19, SARS and MERS were caused by viruses entirely new to humans, and adult immune systems were unused to dealing with entirely new viruses. By and large, the ones that sicken adults year after year are altered versions of viruses they’ve encountered before, such as seasonal flu. Children, on the other hand, are constantly dealing with viruses that are not necessarily novel but are novel to them. “Everything an infant sees, or a young child sees, is new,” says Donna Farber, an immunologist at Columbia University. Thus, their immune system is primed to fight new pathogens in a number of ways.
Babies are born, for example, with a complete repertoire of immune cells called T cells. Every T cell has a unique receptor, and taken together, the pool of millions of T cells can recognize virtually any hypothetical pathogen. As the child begins encountering pathogens, though, their immune system winnows this diverse repertoire. It keeps the T cells involved in fighting off pathogens as a pre-stocked arsenal of “memory T cells,” should those pathogens appear again, but it begins losing the others. This is why adults are able to mount a rapid immune response to previously encountered pathogens, but also why they might have trouble fighting a new one. Diseases such as rubella and chicken pox are also, for various reasons, more severe in adults than in children. The pattern with seasonal flu is different, Farber says, but that may be because immunity against previousu strains of the flu offer some crossover protection in adults.
The same may actually be true for coronaviruses, too, only in children. Another hypothesis for why most kids are spared is that they are frequently infected with the four coronaviruses that cause some common colds. They cold coronaviruses are not as closely related to COVID-19 as SARS or MERS, but they still share some similarities. Immunity against these cold coronaviruses wanes over time, so children who have been recently exposed might have some protection that adults don’t.
Yet another hypothesis has to do with the receptor ACE2, which the new coronavirus uses to enter a cell. The number of ACE2 receptors in the lungs seems to decrease with age, at least according to data in rats. Why would having more ACE2 decrease the severity of COVID-19? No one is quite sure, but ACE2 also seems to have other functions in the body linked to decreased inflammation and scarring, which may protect against severe disease. And in fact, viral infection decreases levels of ACE2. “It’s not going to be as black-and-white as more receptors equal more virus infection, simply because this receptor does other things in the body,” says Kirsty Short, a virologist at the University of Queensland. The story is rather complicated–and illustrative of how science is only starting to understand the virus behind COVID-19.
