Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

SUMMARY Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV- 2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naïve interferon-activated CD4 + T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4 + memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection. HIGHLIGHTS Children have diverse polyclonal SARS-CoV-2-specific naïve T cells Adults have clonally expanded exhausted SARS-CoV-2-specific memory T cells Interferon-activated naïve T cells differentiate into memory T cells in adults but not children Adults but not children develop robust memory T cell responses to SARS-CoV-2