The theory was simple and convincing: children are less vulnerable to the new coronavirus because they carry antibodies to other common coronaviruses that cause the common cold. The idea may also explain why some people infected with the new virus have mild symptoms, while others – presumably without antibodies to the common cold coronavirus – are affected much more severely.
The notion gained strength mainly among people who claimed that this existing protection would quickly lead human populations to herd immunity, the point at which the spread of a pathogen is stopped as it runs out of hosts to infect. A study in the journal Science, published in December, gave a strong boost to the hypothesis.
But for all its appeal, the theory is unsupported, according to a new study published Tuesday in the journal Cell. Based on carefully conducted experiments with live viruses and hundreds of blood samples taken before and after the pandemic, the new research refutes the idea that antibodies to seasonal coronaviruses have any impact on the new coronavirus, called SARS-CoV-2 .
“Going into this study, we thought we would learn that individuals who had pre-existing pre-pandemic antibodies against SARS-CoV-2 would be less susceptible to infection and would have less severe Covid-19 disease,” said Scott Hensley, an immunologist from the University of Pennsylvania. “This is not what we found.”
He and his colleagues concluded that most people are exposed to seasonal coronaviruses at age 5. As a result, about one in five people carry antibodies that recognize the new coronavirus.
But these antibodies are not neutralizing – they cannot defuse the virus or mitigate the severity of symptoms after infection, the team found.
The researchers also compared the antibodies to the common cold coronaviruses in children and adults and found no difference in quantities. In contrast, the Science study reported that about 5% of adults carried these antibodies, compared with 43% of children.
That study “reported very high levels of neutralizing pre-pandemic cross-reactive antibodies in children, something we didn’t find,” said Hensley. (“Cross-reactivity” refers to antibodies capable of attacking similar sites in more than one type of virus.)
“Honestly, I don’t have an explanation for the difference from the Science study,” he added.
Perhaps the difference in locations – Pennsylvania, in his study, versus Britain in previous research – could explain part of the discrepancy, he said.
Other experts said they found Dr. Hensley’s study more convincing of the two and more consistent with the circumstances in which large groups of people were infected with the new coronavirus.
For example, a single person infected with the new coronavirus at a summer camp in Wisconsin triggered an outbreak that affected 76% of other participants, noted John Moore, a virologist at Weill Cornell Medicine in New York.
Likewise, in a fishing trawler that left Seattle for the sea, only three sailors who had antibodies to the new coronavirus before the trip remained free of the virus. These are not the infection rates you would see if protective antibodies were widely distributed in the population, said Dr. Moore.
“The idea that sniffing a while ago somehow protects you from SARS-CoV-2 infection has always left me indifferent, but it has been a persistent urban legend during the pandemic,” he said. “Hopefully, this new paper will finally cool everyone down and put those thoughts in the freezer.”
The experts also praised the new study’s careful and rigorous approach.
“It is great to have a study so well done,” said Shane Crotty, a virologist at the La Jolla Immunology Institute in San Diego.
The theory that existing antibodies can protect people against the new virus “definitely has strong appeal because, at first glance, it can explain a lot about the pandemic,” said Dr. Crotty. “But a beautiful idea doesn’t make it true.”
Dr. Hensley and his colleagues examined samples from 251 people who donated blood to the University of Pennsylvania before the pandemic and then developed Covid-19.
These people carried levels of antibodies capable of recognizing the new coronavirus that were no different from those seen in blood samples collected from 251 people who remained uninfected. And the levels showed no relationship with the clinical outcome in any of the patients.
“It is difficult to find this type of sample – I was simply impressed,” said Marion Pepper, an immunologist at the University of Washington in Seattle. “It’s like three different studies combined into one.”
The most important part of the coronavirus is the spike protein on its surface, which attaches itself to human cells. The peak is also the most distinct part of the virus, so it makes sense that antibodies to seasonal viruses are unlikely to recognize and disarm it, said Pepper.
“There are very specific parts of these viruses that are critical for infection, and most of that cross-reactivity is not directed at those parts,” she said.
But George Kassiotis, an immunologist at the Francis Crick Institute in London who led the study published in Science, disagreed with the findings of the new research. It “confirms in large part, rather than contradicting our main findings,” he said, adding that the new study was too small to rule out any role for existing antibodies.
But even if people do carry antibodies to the coronavirus of childhood infections, the protection they provide is not powerful enough to make a difference, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.
“If there is no measurable effect in a study of hundreds of people in the infected and uninfected groups, then the effect is certainly minimal,” said Bloom.
Most vaccines developed for the new coronavirus focus on the peak protein. Some scientists have argued that antibodies to other parts of the virus may also be essential for protection. But the new study suggests that the other antibodies are of minimal importance in protecting people from SARS-CoV-2.
All experts said the new study does not rule out the role of immune cells, called memory B cells and T cells, produced in response to seasonal coronaviruses. These cells can recognize parts of the new virus and attack it, decreasing the severity of symptoms.
Still, the cells would not prevent infection, said Crotty. When exposed to the new virus, immune cells can be activated “fast enough that you have an asymptomatic infection you never noticed,” he said. “But no, they wouldn’t stop the infection.”
T-cell tests are laborious and expensive, so analyzes of their contribution to immunity are not yet complete. In the meantime, the new study at least rules out a significant role for existing antibodies, said Hensley: “We kind of wrote a chapter here, but there is still a lot to be learned.”