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

Abstract

Children and youth infected with SARS-CoV-2 have milder disease than do adults and, even among those with the recently described multi-system inflammatory syndrome (MIS-C), mortality is rare. The reasons for the differences in clinical manifestations are unknown, but suggest that age-dependent factors may modulate the anti-viral 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 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 IL-17A and IFN-γ, but not 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 COVID-19 patients. 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.

The known unknowns of T cell immunity to COVID-19

“…Interestingly, females seem to mount a somewhat stronger T cell activation following SARS-CoV-2 infection (13) and disruption of T and B cell coordination has been implicated in elderly patients with severe COVID-19 (14). On the other end of the age spectrum, decreased frequencies of IFNγ + CD4 + and CD25 + CD4 + T cells have been described in hospitalized pediatric patients, who have shorter lengths of stay compared with their adult counterparts (15). In conjunction with age and sex, host and viral factors probably also play a role in the early immune defense and coordination of the early SARS-CoV-2-specific T cell response.…”

Inflammatory syndromes associated with SARS-CoV-2 infection: dysregulation of the immune response across the age spectrum

“…Children are thought to be less susceptible than adults to SARS-CoV-2 (9), and COVID-19 has been documented much and (e) absence of chronic comorbidities that compromise the integrity of the vascular endothelium (13).…”

“…While the specific mechanism or mechanisms that protect children from severe COVID-19 are unclear (13), there are five leading theories. Compared with older adults, younger individuals may have (a) a more robust innate immune response during early infection that allows for early control of viral replication; (b) a less robust matory syndrome, children and adults with MIS-C/A present more often with gastrointestinal symptoms and less often with respiratory symptoms and thrombotic sequelae.…”

COVID-19 in Children: A Review and Parallels to Other Hyperinflammatory Syndromes

“…Moreover, some individuals with mild SARS-CoV-2 infection develop T cell responses in the absence of antibody seroconversion (45). In addition, a recent study examining immune responses in pediatric compared with adult patients with COVID-19 infection (and for pediatrics, acute COVID-19 and MIS-C patients were included) found that adults with COVID-19 were more likely to have neutralizing antibody titers compared with children, as well as lower IL-17A and interferon gamma responses, and children in this study did not have differences in anti-spike antibody titers when compared to adults (63). Of note, some of these studies so far have relatively small numbers and larger studies to clarify the immune response profile distinctions amongst children with acute COVID-19 compared with MIS-C compared with adults with acute COVID-19 (severe and less severe/asymptomatic) are needed, especially in the context of the COVID-19 vaccine development efforts.…”