The data stops short of explaining why children develop a milder form of illness. But older research conducted on the SARS-CoV-2 virus’ genetic relative, the coronavirus that caused the 2002-2003 SARS outbreak, lends some clues. It also ravaged adults more than children. That global outbreak killed 774 people, or about one in 10 of those SARS infected. Not a single person under the age of 24 died.
In severe cases of SARS, a patient would initially have a fever and cough while the virus was rapidly replicating in their lungs. About a week later, they’d spontaneously improve, as their immune system kicked in. But then a second phase of the disease would start, which would be much worse than the first. One study by researchers at the University of Hong Kong focusing on 75 SARS patients found that the second stage, the one that often led to death, wasn’t caused by the virus at all, but by patients’ runaway immune systems. For reasons that still aren’t clear, some people, especially the old and sick, weren’t able to turn off their inflammatory response, leading immune cells and inflammation-inducing molecules known as cytokines to flood into the lungs. This so-called “cytokine storm” caused the most severe symptoms of the disease: pneumonia, difficulty breathing, and organ damage.
“These cytokines are supposed to help the immune system clear the virus, but in the people that did poorly the response was overly exuberant, causing more damage than the virus itself,” says Stanley Perlman, a virologist and pediatric infectious disease specialist at the University of Iowa.
Covid-19 appears to have some similarities, so doctors have wondered if limiting this inflammation would be helpful. In one of the first studies of Covid-19 patients, doctors at the Zhongnan Hospital of Wuhan University in Hubei reported that nearly half received steroids, which tamp down an immune response. Though the study’s ability to assess outcomes was limited, the authors reported that no treatments proved effective.
Perlman says scientists still don’t know exactly why some people respond this way. But in studies with mice, his lab discovered that as animals age, their lungs take on damage that leads to structural changes that make them more susceptible to coronavirus infections. With SARS in particular, the older the mice, the sicker they got. “We know the lung environment really matters with this class of respiratory viruses,” says Perlman. “As people age, that lung environment changes. It gets pelted with pollen and pollution and the body responds with inflammation. A history of inflammation may impact how well you do with coronaviruses.”
More research is needed, but it’s a plausible explanation for Covid-19’s mild symptoms in children, says Creech. “The non-inflamed lung is a much less hospitable place for any virus to land,” he says. The next step would be to look at how children with less pristine lungs are faring in the outbreak—like kids with a history of asthma or babies who are born prematurely and lack a substance that helps keep open the tiny sacs in the lungs that exchange oxygen. If these kids experience severe Covid-19 symptoms too, then the “pristine lung” hypothesis holds up.
Another (highly speculative) possibility, says Creech, is that somehow kids may be leveraging their previous immune responses to the cold-causing coronaviruses they’re constantly being assaulted with. “Each of us is a little different in how we can modify the tips of our antibodies to latch on to foreign invaders,” says Creech. “It’s possible that recent coronavirus exposure in kids has led to the emergence of antibodies that have some cross-reactivity with the virus that causes Covid-19.” But, he stresses, so far there’s no evidence that’s what’s going on.