Stanford pediatric immunologist Lawrence Steinman, MD, was puzzled. Reading the COVID-19 pandemic statistics, he asked himself: "Is there any other infectious agent that appears to be less dangerous to children than to adults?"
He couldn't think of one. So he started investigating, teaming with researchers from Stanford, Columbia and Yale universities.
The resulting Proceedings of the National Academy of Sciences perspective piece compiles a list of likely biological factors underlying the reduced development of COVID-19 for children compared to adults.
As the authors note, it's not that kids can't get COVID-19. They can and they have -- but less frequently than adults. And they can get very sick from it -- but that happens less often than with grown-ups. A severe multisystem inflammatory syndrome in children, abbreviated MIS-C, has been associated with COVID-19, but it's blessedly rare and carries a mortality rate below 2%.
Children ages 17 and younger constitute 22.4% of the American population; as of Sept. 3, they make up less than 10% of the country's total COVID-19 cases. The number of cases has increased significantly in recent months and continues to rise. Yet, children still account for fewer than 0.1% of total deaths in the U.S. from COVID-19, and their rate of hospitalization for the disease is far lower.
A number of possible reasons are reported in the PNAS perspective. Two stand out as posing, to me, exceptionally clear and logical explanations for COVID-19's relatively low impact on children.
First, the SARS-CoV-2 virus has a harder time infecting a kid's tissues than an adult's, because it has fewer entry routes.
To hack into a cell, a virus first needs to hook onto a surface molecule on that cell. The receptors that SARS-CoV-2 latches onto are found on cells in many tissues throughout the body, including on cells in the nasal passages (where infection begins) and in the lungs (where it ends up if the virus is lucky and you're not). The virus can get a toehold on these cells, enter them and convert them into factories cranking out copies of itself. These baby viruses then bust out of the spent cells and head for new ones to hijack and pillage.
But guess what? The target cells in kids' noses have fewer of these particular viral receptor proteins on their surfaces than grown-ups' equivalent cells do. Ditto for the target cells in young lungs. So, SARS-CoV-2 has a harder time spreading within and among those tissues in children.
Second, kids spend a fair amount of time with the sniffles. Young children get up to half a dozen common colds a year, a fair percentage of them caused by coronaviruses that are close cousins to SARS-CoV-2. Those relatively benign viruses are similar enough to SARS-CoV-2 that the immune response the body mounts to fend them off might also impede infection of the nasal passages by SARS-CoV-2 and slow its consequent spread to the lungs.
"Most of us consider colds a real nuisance," Steinman told me. "But these bothersome viral infections may be doing a heck of a lot of good. The cross-reactive immunity they trigger could keep the really bad bug from getting a grip on our lungs."
Although the evidence collected so far conjures up some implications, Steinman and his co-authors acknowledge that many questions remain.
An important one: Might kids possibly be great transmitters of the virus? Studies have shown that exposed children under age 5 carry higher amounts of SARS-CoV-2 in their nasal passages than similarly exposed older kids or adults, although scientists have not yet pinpointed a definitive explanation. So the possibility that young children can spread the coronavirus around can't yet be ruled out.
Steinman and his co-authors noted carefully in the perspective piece: "We do not know how the carrier status of children affects their caregivers."
The answer to this and other questions will have implications for educators tasked with deciding when to resume in-person classes; however, Steinman and his co-authors also write that social distancing has downsides for children.
Reduced interaction, impaired play and closed playgrounds (where kids used to trade viruses freely) can affect psychological health, educational progress, social and behavioral development -- and even body weight. Not to mention the impact of skipped routine medical and dental care and lower vaccination rates.
As Steinman pointed out, "This virus doesn't have to infect children to affect them."