The outbreak of a new virus always breeds confusion. Where did it come from? How does it spread? How dangerous is it? Ten weeks into the Covid-19 epidemic, enough information has emerged to start filling in some of these gaps. Scientists believe the virus that causes the respiratory disease is likely to be transmitted in droplets through coughing. The available data suggests that a single contagious person will infect about 2.2 others, on average. Globally, 3.4 percent of reported Covid-19 patients have died, though that fatality rate is likely inflated, since people with mild symptoms are probably not being diagnosed and counted in the overall patient pool.
But as the weeks have gone by, one mystery has remained: Where are all the kids?
In a recent analysis by a team of researchers at Johns Hopkins and in China of more than 72,000 confirmed cases from China, children under the age of 10 accounted for less than 1 percent of all infections. Of the 1,023 deaths recorded in China at the time, not a single child was among them. “We see relatively few cases among children,” World Health Organization director general Tedros Adhanom Gheberyesus told reporters in mid-February. “More research is needed to understand why.”
Plus: How can I avoid catching it? Is Covid-19 more deadly than the flu? Our in-house Know-It-Alls answer your questions.
“It’s really very weird,” says Buddy Creech, an infectious disease pediatrician at the Vanderbilt University Medical Center. Mortality patterns associated with most respiratory pathogens traditionally form a U-shaped curve, reflecting more severe disease in the very young and the elderly, says Creech. Respiratory viruses flourish in bodies where the immune system is either still developing or has started to wear out. These include the four coronaviruses that cause the common cold, which tend to be way more common in children than adults. “The new virus that causes Covid-19 appears to flip that,” says Creech.
Now, a detailed new study helps to explain what’s been going on. It turns out, it’s not that kids are somehow immune to SARS-CoV-2. They’re just not getting very sick.
“Kids are just as likely to get infected as adults,” says Justin Lessler, an infectious disease epidemiologist at Johns Hopkins Bloomberg School of Public Health, who co-led the new study with epidemiologists at the Harbin Institute of Technology in Shenzhen and the Shenzhen Center for Disease Control and Prevention. “If you only have data on cases, which is most of what’s out there, you can’t figure out whether an exposed kid is more likely to get infected than an exposed adult. Nobody besides us has been able to look at data on groups of exposed people to see who got sick and who didn’t.”
A few weeks ago, Lessler was contacted by a Johns Hopkins alumnus currently working in China about collaborating on disease modeling using data collected by the Shenzhen CDC. Once he got a look at the data, Lessler realized it could help answer this question about how the virus acts in different age groups.
On January 8, the Shenzhen CDC identified its first local case of Covid-19 and began monitoring travelers from Hubei province, the center of the outbreak 700 miles to the north. Over the next few weeks, the agency expanded its surveillance, testing people with fevers in hospitals and local clinics. Altogether, public health officials identified 391 Covid-19 patients and 1,286 people who’d been in close enough contact to these patients to be exposed to the virus. They followed these contacts, testing them regularly to see whether they contracted the disease, even if they never showed symptoms. The team found that children ages 9 and younger who had been exposed to the virus were just as likely to be infected as other age groups—between 7 and 8 percent of the time. But they were much less likely to have the kinds of severe symptoms seen in older groups. In fact, many kids never showed symptoms at all. The researchers posted their analysis to the medRxiv preprint server on Wednesday.
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.
It may take years of careful experimentation before scientists figure out the mechanism behind why Covid-19 seems less damaging to kids. But Lessler’s research has clear implications for public health interventions now. If kids can get infected, they can likely play a role in further spreading the disease, because their milder symptoms may go undetected. “If we thought that kids weren’t getting infected, then closing schools might be creating undue hardship for people with no real upside,” says Lessler. “But the data suggests that closing schools might be an important thing to do to prevent onward transmission.”
As case numbers continue to rise in the US, public health officials will soon be confronted with a choice over which kinds of social distancing strategies to deploy to contain local outbreaks. It may be time to keep the kids at home.
Read all of our coronavirus coverage here.
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