When COVID-19 swept the globe at the beginning of 2020, it soon became clear that the disease hit some much harder than others. Early on in the pandemic, it became apparent that age was a major factor influencing the severity of disease, with the oldest adults most at risk of serious complications and death. At the other extreme, children seem to be largely unaffected by SARS-CoV-2 infection, with most experiencing only mild symptoms or none at all.
Figuring out the mystery of why COVID-19 strikes the old but spares the young could help us identify at-risk individuals, inform the prioritization of vaccination programs and even give us a sense of how long a protective response might last, explained Elizabeth Tham, a Principal Investigator at A*STAR’s Singapore Institute for Clinical Sciences (SICS). Tham is also a Consultant Pediatrician and Head of the Allergy, Immunology and Rheumatology division at the Department of Pediatrics, National University Hospital (NUH).
“This understanding could lay the groundwork for future therapeutics such as convalescent plasma infusions, monoclonal antibodies and vaccine development. It will also impact clinical decision making and healthcare policy including decisions on screening, quarantine and the closure of schools and workplaces,” Tham said.
In a review of the proposed mechanisms behind the age-related differences in responses to SARS-CoV-2, Tham and her colleagues from A*STAR and NUH found that the relatively immature immune systems of children offered them some protection against the disease.
Children’s regulatory T cells exert stronger effects than those found in adults, she said, and their limited pro-inflammatory responses also mean that they are less likely to overproduce cytokines, a feature that is associated with severe lung damage in adults. “The innate immune response in children is also different from adults, with increased activation of neutrophils and decreased circulating monocytes, dendritic cells and natural killer cells,” Tham added.
However, when children develop symptoms of COVID-19, they can be life-threatening. One such condition is a multisystem inflammatory syndrome in children (MIS-C), a post-inflammatory or autoimmune process where the initial infection triggers a systemic immune response. Although the mechanism behind MIS-C is still unclear, the emerging data suggest a possible genetic predisposition as it appears to strike children from certain ethnic groups more frequently than others.
While our understanding of COVID-19 and how it impacts children have come a long way since the pandemic was first recognized, more studies are required for a fuller understanding of the immune response in different age groups, Tham said. To that end, Tham is collaborating with researchers at NUH, the National University of Singapore, and Duke-NUS Medical School to evaluate the role of cross-reactive neutralizing antibodies from seasonal coronaviruses in modulating responses to SARS-CoV-2 in both children and adults, and also to study the longevity of antibody responses in previously COVID-19-infected children.
The A*STAR researchers contributing to the study are from the Singapore Institute for Clinical Sciences (SICS).