It's been a big puzzle of the pandemic: Why are children so much less likely than adults to become infected with the new coronavirus and, if infected, less likely to become ill?
A possible reason may be that many children already have antibodies to other coronaviruses, according to researchers at the Francis Crick Institute in London. About 1 in 5 of the colds that plague children are caused by viruses in this family. Antibodies to those viruses may also block SARS-CoV-2, the new coronavirus causing the pandemic.
In a study published on 6 November in Science, the group, led by George Kassiotis, who heads the Retroviral Immunology Laboratory at the institute, reports that on average only 5% of adults had these antibodies, but 43% of children did.
Researchers who did not participate in the study were intrigued by the finding. H. Benjamin Larman, an immunologist at Johns Hopkins School of Medicine, called it a "well-done study that puts forward a compelling theory which is supported by their data."
Stephen J. Elledge, a genetics professor at Harvard Medical School and Brigham and Women's Hospital, had a similar response. He and others have found that many people have antibodies to common colds caused by other coronaviruses; in laboratory studies, these antibodies also block the new coronavirus.
In March, as the pandemic was just beginning, Kassiotis and his colleagues decided to develop a highly sensitive antibody test. To assess it, they examined blood samples taken before the pandemic from over 300 adults and 48 children and adolescents, comparing them with samples from more than 170 people who had been infected with the new coronavirus.
The scientists expected samples taken before the pandemic to have no antibodies that attacked the new coronavirus. Those were to be the controls for the test the scientists were developing.
Instead, they found that many children, and some adults, carried one antibody in particular that can prevent coronaviruses, including the new one, from entering cells. This antibody attaches itself to a spike that pokes out of coronaviruses.
While the tip of the spike is unique to the new coronavirus, the base is found in all coronaviruses, Kassiotis said. In lab tests, antibodies to the base of the spike prevented the new coronavirus from entering cells in order to reproduce.
Now the researchers are planning to expand their study to monitor thousands of children and adults. Some have antibodies that can block the new coronavirus in lab tests. Others do not.
"If they have the pandemic strain, are they protected?" Kassiotis asked.
Will they get sick, he wondered, or will the infection be all but undetectable?
Elledge and his colleagues at Harvard developed their own highly specific, sensitive and exhaustive antibody test, VirScan. It is able to detect a diverse collection of antibodies with that are directed at any of more than 800 places on the new coronavirus, including the antibody that Kassiotis and his colleagues studied.
After examining blood taken from 190 people before the pandemic emerged, Elledge and his colleagues concluded that many already had antibodies, including the one targeting the base of the spike - presumably from infections with related coronaviruses that cause colds.
But while adults might get one or two colds a year, Elledge said, children may get up to a dozen. As a result, many develop floods of coronavirus antibodies that are present almost continuously; they may lessen cold symptoms, or even leave children with colds that are symptomless but still infectious.
While adults may not have detectable coronavirus antibodies, many may be able to quickly make antibodies if they are infected with a coronavirus.
In typical viral infections, the immune system pours out antibodies to fight the virus. When the infection is quelled, the antibodies, no longer needed, diminish in number. But the body is left with so-called memory cells that allow antibody production to soar rapidly if the virus tries to invade again.
The mystery of memory cells
Then why do we have a pandemic? Shouldn't most of us be protected by memory cells left by other coronavirus infections?
"It is quite possible that you lose your memory over time," Elledge said.
He suspects that the new coronavirus may interfere with the activation of the memory cells able to respond to the infection.
An infection "might give you a hazy memory that fades over time," he said. If so, a very recent infection with a common cold coronavirus would be needed to protect against the new coronavirus, and even then the protection might last only for a limited time.
The new coronavirus would have hobbled the production of antibodies that specifically attack it. That might explain why children, with their seemingly continuous colds, are much better off than adults.
Elledge said that if he is right about the loss of memory cells, that bodes well for vaccines. A vaccine boosts antibody production without the presence of a virus. So the virus "is not in the background, messing up memory cell formation," he said.
Another possibility is that most adults actually are protected by memory cells from previous infections with the common cold. Although few have enough antibodies in their blood to protect them at any given time, they may be able to quickly make antibodies to lessen the impact of the new coronavirus.
That might explain why many adults who are infected recover quickly.
"We focus on those who get really sick, but 95 to 98% of those who get the virus don't have to go to the hospital," Elledge said. "There are a lot of people who do get better."
That happened to Larman and his family of five. Four of them got sick with COVID-19, the illness caused by the new coronavirus, in July. None were seriously ill, and his 4-year-old son was spared altogether.
"My son was not isolated from us and therefore heavily exposed," Larman said. "He tested negative twice, and so we certainly suspect that he had some form of preexisting immunity."