Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients

Abstract

Differences in immune responses to SARS-CoV-2 in children and adults are linked to clinical outcomes.

Elucidating immune responses in COVID-19

Compared to adults, young people with COVID-19 have milder disease. Pierce et al. compared immune responses in hospitalized adult and young patients with COVID-19 to identify potential contributing mechanisms. In the first week after hospitalization, circulating IL-17A and IFN-γ concentrations were inversely related to age. More than 3 weeks later, CD4 ⁺ T cell responses to viral spike protein were higher in adult compared to younger patients. Neutralizing antibody titers were also higher in adults and correlated positively with age and negatively with IL-17A and IFN-γ. These findings suggest that the poor outcome in adults is not caused by a failure to generate adaptive immune responses.

Abstract

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) ( n = 65) and adult ( n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor–α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25 ⁺ on CD4 ⁺ T cells and the frequency of IFN-γ ⁺ CD4 ⁺ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.