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 J Zaunders; José Alquicira-Hernandez; Seyhan Yazar; Stephanie Ruiz-Diaz; Mandeep Singh; Rama Dhenni; Wunna Kyaw; Fiona Tea; Vera Merheb; Fiona X Z Lee; Rebecca Burrell; Annaleise Howard-Jones; Archana Koirala; Li Zhou; Aysen Yuksel; Daniel R 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 D Sprent; Joseph E Powell; Fabienne Brilot; Ralph Nanan; Peter S Hsu; Elissa K Deenick; Philip N Britton; Tri Giang Phan

doi:10.1016/j.clim.2022.109209

Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19

Clin Immunol. 2023 Jan:246:109209. doi: 10.1016/j.clim.2022.109209. Epub 2022 Dec 17.

Authors

Weng Hua Khoo¹, Katherine Jackson², Chansavath Phetsouphanh³, John J Zaunders⁴, José Alquicira-Hernandez⁵, Seyhan Yazar⁶, Stephanie Ruiz-Diaz², Mandeep Singh¹, Rama Dhenni¹, Wunna Kyaw¹, Fiona Tea⁷, Vera Merheb⁷, Fiona X Z Lee⁷, Rebecca Burrell⁸, Annaleise Howard-Jones⁹, Archana Koirala⁹, Li Zhou⁹, Aysen Yuksel⁹, Daniel R Catchpoole¹⁰, Catherine L Lai⁹, Tennille L Vitagliano⁹, Romain Rouet¹, Daniel Christ¹, Benjamin Tang¹¹, Nicholas P West¹², Shane George¹³, John Gerrard¹⁴, Peter I Croucher¹, Anthony D Kelleher³, Christopher G Goodnow¹⁵, Jonathan D Sprent¹, Joseph E Powell¹⁶, Fabienne Brilot¹⁷, Ralph Nanan¹⁸, Peter S Hsu¹⁰, Elissa K Deenick¹⁹, Philip N Britton²⁰, Tri Giang Phan²¹

Affiliations

¹ Garvan Institute of Medical Research, Sydney, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia.
² Garvan Institute of Medical Research, Sydney, Australia.
³ Kirby Institute, UNSW Sydney, Sydney, Australia.
⁴ Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia.
⁵ Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
⁶ Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia.
⁷ Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
⁸ Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁹ Kids Research, The Children's Hospital at Westmead, Sydney, Australia.
¹⁰ Kids Research, The Children's Hospital at Westmead, Sydney, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Sydney, Australia.
¹¹ Department of Intensive Care Medicine, Nepean Hospital, Sydney, Australia; Centre for Immunology and Allergy Research, The Westmead Institute for Medical Research, Sydney, Australia; Respiratory Tract Infection Research Node, Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney, Australia.
¹² Systems Biology and Data Science, Menzies Health Institute QLD, Griffith University, Parklands, Australia.
¹³ Departments of Emergency Medicine and Children's Critical Care, Gold Coast University Hospital, Southport, QLD, Australia; School of Medicine and Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia.
¹⁴ Department of Infectious Diseases and Immunology, Gold Coast University Hospital, Southport, QLD, Australia.
¹⁵ Garvan Institute of Medical Research, Sydney, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia; UNSW Cellular Genomics Futures Institute, UNSW Sydney, Sydney, Australia.
¹⁶ Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia; UNSW Cellular Genomics Futures Institute, UNSW Sydney, Sydney, Australia.
¹⁷ Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia; Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, Australia; Brain and Mind Centre, The University of Sydney, Sydney, Australia.
¹⁸ Charles Perkins Centre Nepean, University of Sydney, Sydney, Australia.
¹⁹ Garvan Institute of Medical Research, Sydney, Australia; Faculty of Medicine, UNSW Sydney, Sydney, Australia.
²⁰ Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; The Children's Hospital at Westmead, Sydney Children's Hospitals Network, Sydney, Australia.
²¹ Garvan Institute of Medical Research, Sydney, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia. Electronic address: t.phan@garvan.org.au.

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.

Keywords: COVID-19; Clonal dynamics; Interferon-activated naive T cells; Memory T cells; SARS-CoV-2; Single cell transcriptomics; T cell receptor repertoire.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Viral
CD4-Positive T-Lymphocytes
COVID-19*
Humans
Immunity, Cellular
Lymphocyte Activation
SARS-CoV-2

Substances

Antibodies, Viral