When a six-month-old baby was admitted to a California hospital last month with fever and blotchy rash, the doctors diagnosed a classic case of Kawasaki disease.
The inflammatory condition that causes swelling in the blood vessels affects about one in 200 US children, with its tell-tale signs of bloodshot eyes and cracked lips. So it came as a huge shock to the staff at Lucile Packard Children’s Hospital at Stanford when the baby tested positive for coronavirus.
“It came out of the blue,” Dominique Suarez, the doctor who treated the infant, told the Financial Times. “We don’t understand much about Covid-19 in children. Is this association a manifestation of the virus?”
Dr Suarez’s observation, which has been repeated in dozens of hospitals around the world, has exposed one the significant number of unknowns about a virus that leaves the vast majority of children relatively unscathed.
Numerous studies have found that the virus is a mild disease for children. In one of the largest, by doctors in Shanghai, 94 per cent of children with the virus had an asymptomatic, mild or moderate illness. A separate review by the Karolinska Institute in Sweden found that children accounted for fewer than 5 per cent of diagnosed Covid-19 cases globally. Of 2,572 infected children analysed by the Centers for Disease Control and Prevention in the US, 5.7 per cent were hospitalised and three died.
But why children exhibit such mild forms of a virus that has killed almost 265,000 people around the world remains unclear. “Right now it’s still a big mystery,” said Isabella Eckerle, a virologist at the Geneva Centre for Emerging Viral Diseases. “We don’t know what’s going on with the children. They don’t get sick at all, and if they do they’re only mildly sick.”
One reason some adults become seriously unwell with the virus is because their body triggers a huge immune response — a so-called cytokine storm — that can affect the heart and lungs.
“Imagine you have a couple of thieves coming into a village and you bring in an army and some cannons to fight them,” explained Gary Wong, a paediatrics professor at the Chinese University of Hong Kong. “You get rid of the thieves but destroy the village.”
Children’s bodies rarely respond in this way and seem better able to “strike the right balance” between effectively fighting disease and damaging the body, he said.
Why children and adults respond differently remains unclear. One theory is that children are more likely to be exposed to relatively benign coronaviruses at school or nursery, and so they confront Covid-19 with a more effective response.
Yet in an anomaly that underlines the complexity of coronavirus, the massive inflammatory response of the tiny minority of children who develop Kawasaki disease appears to contradict the relatively benign immune response in the vast majority of children with the illness.
The lack of clarity on how the virus affects children has come into focus as governments around the world contemplate whether to reopen schools to ease the lockdown.
In the early days of the outbreak, policymakers believed the virus could spread easily among young people, like any other infectious disease, and so schools were closed around the world to limit transmission.
But recent analysis into how the virus spreads in schools and households has suggested this may not be the case. One Australian study found 18 Covid-positive pupils did not infect any of the 735 children and 128 staff they were in close contact with at school. Another from China found children had been the index, or first case, of Covid-19 in fewer than 10 per cent of households, compared with 54 per cent in a comparable study of swine flu.
Other studies included one co-authored by Dr Eckerle into viral loads — the number of particles carried by a person with the virus — have reached different conclusions.
Generally, a high viral load means people have more serious symptoms and shed more virus particles, making them more infectious. Yet Dr Eckerle’s team found little difference between the viral loads in children and adults despite the former generally having a relatively mild form of the disease.
A separate study at Charité-Universitätsmedizin Berlin, one of Europe’s largest university hospitals, examined thousands of swabs and concluded that children “may be as infectious as adults”. It highlighted concerns that asymptomatic children who did not conform to social distancing and hygiene rules could easily spread the virus, and cautioned against schools reopening.
“Transmission potential in schools and kindergartens should be evaluated using the same assumptions of infectivity as for adults,” wrote the authors that included Christian Drosten, the institute’s director.
Such conflicting science makes it extremely difficult to make informed decisions. The rate of Covid-19 infection rose in Denmark after its schools and kindergartens reopened last month.
“We really need those basic facts about infectiousness in children,” said Jennifer Dowd, deputy director of the Leverhulme Centre for Demographic Science in Oxford.
Prof Wong at the Chinese University of Hong Kong said a more comprehensive understanding of how the virus affected children was meant not just to protect young people: it would help in the pandemic fight more generally by increasing knowledge of the illness. “We want adults to react to the virus the way that children do,” he said.
“All of us are in a learning curve because we’ve never seen a virus behave like this,” Prof Wong said. “We’re learning bit by bit.”