Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19
Type
PreprintAuthor/s
Khoo, Weng HuaJackson, Katherine
Phetsouphanh, Chansavath
Zaunders, John J.
Alquicira-Hernandez, José
Yazar, Seyhan
Ruiz-Diaz, Stephanie
Singh, Mandeep
Dhenni, Rama
Kyaw, Wunna
Tea, Fiona
Merheb, Vera
Lee, Fiona X. Z.
Burrell, Rebecca
Howard-Jones, Annaleise
Koirala, Archana
Zhou, Li
Yuksel, Aysen
Catchpoole, Daniel R.
Lai, Catherine L.
Vitagliano, Tennille L.
Rouet, Romain
Christ, Daniel
Tang, Benjamin
West, Nicholas P.
George, Shane
Gerrard, John
Croucher, Peter I.
Kelleher, Anthony D.
Goodnow, Christopher G.
Sprent, Jonathan D.
Powell, Joseph D.
Brilot, Fabienne
Nanan, Ralph
Hsu, Peter S.
Deenick, Elissa K.
Britton, Philip N.
Phan, Tri Giang
Abstract
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 ...
See moreSUMMARY 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
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See moreSUMMARY 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
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Date
2022Share