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

Abstract

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 naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive 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. HIGHLIGHTSO_LIChildren have diverse polyclonal SARS-CoV-2-specific naive T cells C_LIO_LIAdults have clonally expanded exhausted SARS-CoV-2-specific memory T cells C_LIO_LIInterferon-activated naive T cells differentiate into memory T cells in adults but not children C_LIO_LIAdults but not children develop robust memory T cell responses to SARS-CoV-2 C_LI O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/478400v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@e9586org.highwire.dtl.DTLVardef@17aaf37org.highwire.dtl.DTLVardef@18575e0org.highwire.dtl.DTLVardef@fde4ae_HPS_FORMAT_FIGEXP M_FIG C_FIG