A study of pediatric and adult COVID-19 patients at two New York Hospitals has found that children and adults produce different types and amounts of antibodies in response to the novel virus. Although the findings strongly suggest the course of infection is different, it’s still not known how children are able to avoid and clear the virus so much more easily than adults.
While almost everything about this coronavirus has been novel, researchers were able to determine pretty early on that children are significantly less affected by SARS-CoV-2 than their adult and especially elderly counterparts. And this study from doctors at New York-Presbyterian/Columbia University Irving Medical Center and Morgan Stanley Children’s Hospital of New York provides more evidence as to why that is the case.
“Children are uniquely adapted to see pathogens for the first time. That's what their immune system is designed to do. Children have a lot of naive T cells that are able to recognize all sorts of new pathogens, whereas older people depend more on our immunological memories. We're not as able to respond to a new pathogen like children can,” explained Columbia University immunologist Donna Farber, who co-lead the study.
For the study, published in Nature Immunology, the researchers examined 47 pediatric patients and 32 adults broken into four cohorts—children who were hospitalized with COVID-19-induced multisystem inflammatory syndrome (MIS-C), children who were infected with SARS-CoV-2 but did not develop MIS-C, adults whose mild COVID-19 did not require hospitalization, and hospitalized adults with severe COVID-19. When the researchers looked for SARS-CoV-2 antibodies among each cohort, they recorded radically different results.
Interestingly, despite some children being diagnosed with MIS-C and some not, both pediatric cohorts produced the same antibody profile—which differed from that of adults. While adults produced anti-Spike IgG, IgM and IgA antibodies, as well as anti-nucleocapsid IgG antibodies, children produced mostly IgG antibodies for the Spike protein, not nucleocapsid. These results show pediatric patients produce significantly less anti-SARS-CoV-2 antibodies than their infected adult counterparts.
Of the antibodies children did produce, they all had reduced neutralizing activity; whereas both adults cohorts demonstrated the opposite. In fact, the sickest adults had the most neutralizing activity.
“There is a connection between the magnitude of your immune response and the magnitude of the infection: The more severe the infection, the more robust the immune response, because you need to have more immune cells and immune reactions to clear a higher dose of a pathogen,” said Farber.
In contrast to adults, children also produced very few antibodies against a viral protein that is only visible to the immune system after the virus infects human cells. Farber said this suggests that children do not experience widespread infection when they contract COVID-19. In other words, the virus doesn’t kill a lot of their cells so they do not need a strong antibody response to clear it. Although further research is needed, a reduced course of infection in children could signify they are infectious for a shorter period of time—data that is consistent with previous findings regarding host children.
Even with this data, the researchers stress there is still a lot to be learned about the novel coronavirus. To that end, they are looking into the differences in T-cell response between children and adults. Children infected with SARS-CoV-2 may generate a stronger response from the innate immune system. If the innate response is really strong, Farber says it can “reduce the viral load in the lungs, and the antibodies and T cells of the adaptive response have less to clear up.”
It's also possible that the virus is less able to infect children's cells, possibly because children's cells express fewer proteins the virus needs to infect humans. The research team is now testing these possibilities with cells from children versus adults.
“There are still all these issues that we have very little information about," said study co-author Matteo Porotto, associate professor of viral molecular pathogenesis in Columbia's Department of Pediatrics. "The interaction between the virus and the host is the reason why we see so much diversity in responses to this virus, but we don't understand enough about this virus yet to really determine what leads to severe disease and what leads to mild disease."