Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19
Weng Hua Khoo, Katherine Jackson, Chansavath Phetsouphanh, John Zaunders, José Alquicira-Hernández, Seyhan Yazar, Stephanie Ruiz‐Diaz, Mandeep Singh, Rama Dhenni, Wunna Kyaw, Fiona Tea, Vera Merheb, Fiona X. Z. Lee, Rebecca Burrell, Annaleise R. Howard‐Jones, Archana Koirala, Li Zhou, Aysen Yuksel, Daniel Catchpoole, Catherine L. Lai, Tennille L. Vitagliano, Romain Rouet, Daniel Christ, Benjamin Tang, Nicholas P. West, Shane George, John Gerrard, Peter I. Croucher, Anthony D. Kelleher, Christopher G. Goodnow, Jonathan Sprent, Joseph E. Powell, Fabienne Brilot, Ralph Nanan, Peter Hsu, Elissa K. Deenick, Philip N Britton, Tri Giang Phan
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 naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This 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.