Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept. 18 in the journal Science Translational Medicine.
A widespread and dangerous immune response to the virus has been linked to acute respiratory distress syndrome, the need for ventilation, and increased mortality in adults with COVID-19. These outcomes are less common in children, which has led to speculation that immune system response to the virus is somehow suppressed. But the new study, which examined serum and cell samples obtained from pediatric and adult patients diagnosed with COVID-19, found that children actually express higher levels of two specific immune system molecules. The researchers believe this may contribute to the better outcomes.
“To our surprise, we found these particular serum cytokines were at higher levels in children than adults,” said Kevan Herold, the C.N.H. Long Professor of Immunology and Internal Medicine at Yale and co-senior author of the paper.
Intriguingly, the analysis also showed that certain types of antibody responses thought to be protective were actually higher in adults, including those with severe cases, than in children, the research found.
Since the earliest days of the COVID-19 outbreak, scientists have observed that children infected with the virus tend to fare much better than adults. To determine why that is, Herold, along with his spouse, Betsy Herold, the co-senior author and a professor of pediatrics and microbiology-immunology at Albert Einstein College of Medicine, decided to study blood and cell samples collected from patients of different ages who were admitted with COVID-19 symptoms to the Montefiore Medical Center in New York City.
Specifically, they looked for variations in the types of immune system responses in patients who experienced different health outcomes from the novel coronavirus. The subjects also included children and adolescents diagnosed with multi-system inflammatory syndrome or MIS-C, a rare complication of COVID-19 infection in young people that is associated with a variety of severe health complications.
They found that levels of two immune system molecules — interleukin 17A (IL-17A), which helps mobilize immune system response during early infection, and interferon gamma (INF-g), which combats viral replication — were strongly linked to the age of the patients. The younger the patient, the higher the levels of IL-17A and INF-g, the analysis showed.
These two molecules are part of the innate immune system, a more primitive, non-specific type of response activated early after infection, Kevan Herold noted. Conversely, the adults showed a more vigorous adaptive immune system response including higher neutralizing antibody levels, which record signatures of pathogens and target them for elimination.
They also found that children with rare cases of MIS-C also have high levels of IL-17A and INF-g, but seldom exhibit severe damage to lung tissue that characterizes severe adult cases. These children, however, share other immune response signatures linked to more severe adult cases. The source of the IL-17A and INF-gmolecules remain unknown, but its identification may shed light on cells that can be targeted to prevent severe effects from COVID-19.
Boosting certain types of immune responses may be beneficial to patients, the authors theorize.
“The suggestion is that kids have a more robust, earlier innate immune response to the virus, which may protect them from progressing to severe pulmonary disease,” Betsy Herold said.
- Carl A. Pierce, Paula Preston-Hurlburt, Yile Dai, Clare Burn Aschner, Natalia Cheshenko, Benjamin Galen, Scott J. Garforth, Natalia G. Herrera, Rohit K. Jangra, Nicholas C. Morano, Erika Orner, Sharlene Sy, Kartik Chandran, James Dziura, Steven C. Almo, Aaron Ring, Marla J. Keller, Kevan C. Herold, Betsy C. Herold. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Science Translational Medicine, 2020; eabd5487 DOI: 10.1126/scitranslmed.abd5487