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SARS-CoV-2 Infection in Children Does Not Necessitate Establishment of Adaptive SARS- CoV-2-Specific Immunological Memory

49 Pages Posted: 4 Nov 2021 Publication Status: Accepted

See all articles by Louise C. Rowntree

Louise C. Rowntree

University of Melbourne - Department of Microbiology and Immunology (DMI)

Thi H. O. Nguyen

University of Melbourne - Department of Microbiology and Immunology (DMI)

Lukasz Kedzierski

University of Melbourne - Department of Microbiology and Immunology (DMI)

Melanie R. Neeland

Murdoch Children's Research Institute - Infection and Immunity

Jan Petersen

Monash University - Infection and Immunity Program and Department of Biochemistry and Molecular Biology

Jeremy C. Crawford

St Jude Children’s Research Hospital - Department of Immunology

Lilith F. Allen

University of Melbourne - Department of Microbiology and Immunology

Anastasia A. Minervina

St. Jude Children's Research Hospital - Department of Immunology

Mikhail V. Pogorelyy

St. Jude Children's Research Hospital - Department of Immunology

Priyanka Chaurasia

Monash University - Infection and Immunity Program

H T

University of Melbourne - Department of Microbiology and Immunology

Adam K. Wheatley

University of Melbourne - Department of Microbiology and Immunology (DMI)

Hayley A. McQuilten

University of Melbourne - Department of Microbiology and Immunology

E. Bridie Clemens

University of Melbourne - Department of Microbiology and Immunology (DMI)

Fatima Amanat

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Florian Krammer

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Sabrina Sonda

University of Tasmania - School of Medicine

Katie Flanagan

University of Tasmania - School of Health Sciences and School of Medicine

Paul V. Licciardi

Murdoch Children's Research Institute - Infection and Immunity

Stephen J. Kent

University of Melbourne - Department of Microbiology and Immunology

Jamie Rossjohn

Monash University - Infection and Immunity Program

Paul Thomas

St Jude Children’s Research Hospital - Department of Immunology

Shidan Tosif

Murdoch Children's Research Institute - Infection and Immunity

Nigel W. Crawford

Murdoch Children's Research Institute; Murdoch Children's Research Institute - Infection and Immunity

C. van de Sandt

University of Melbourne - Department of Microbiology and Immunology (DMI)

Katherine Kedzierska

University of Melbourne - Department of Microbiology and Immunology (DMI)

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Abstract

Children are at lower risk of developing severe COVID-19, yet the underlying immune mechanisms are understudied. While children’s innate immunity can drive rapid resolution of SARS-CoV-2 infection, the establishment of SARS-CoV-2-specific T-cell and B-cell memory in COVID-19 children remains unexplored. We recruited a household cohort to understand SARS-CoV-2-specific CD4+ and CD8+ T-cell immune responses at one month after mild or asymptomatic SARS-CoV-2 infection in PCR-positive children in comparison to those found in their mothers. We analysed SARS-CoV-2-specific T-cell responses, together with B-cells, directly ex vivo using six HLA class-I tetramers and one class-II tetramer presenting SARS57 CoV-2 T-cell epitopes (A1/ORF1a1637, A2/S269, A3/N361, A24/S1208, B7/N105, B40/N322 and DPB4/S167), and Spike- and Receptor Binding Domain (RBD)-specific B-cell probes. Our in depth profiling of epitope-specific T-cell responses at quantitative, phenotypic and clonal levels found that only children who seroconverted had prominent memory T-cell and B-cell profiles. These children had a high magnitude of SARS-CoV-2-specific T-cells displaying memory phenotypes and prevalent T-cell receptor motifs, which were not observed in PCR+ RBD but IgG-negative children. This suggests that seroconversion but not PCR-positivity defines establishment of adaptive SARS-CoV-2-specific immunological memory in children. Our study suggests that COVID-19 vaccination of children could be a major advantage in terms of establishing T-cell and B-cell immunological memory, especially in children who did not seroconvert after SARS-CoV-2 infection.

Keywords: COVID-19, T cells, B cells, seroconversion, children, memory T cells

Suggested Citation

Rowntree, Louise C. and Nguyen, Thi H. O. and Kedzierski, Lukasz and Neeland, Melanie R. and Petersen, Jan and Crawford, Jeremy C. and Allen, Lilith F. and Minervina, Anastasia A. and Pogorelyy, Mikhail V. and Chaurasia, Priyanka and T, H and Wheatley, Adam K. and McQuilten, Hayley A. and Clemens, E. Bridie and Amanat, Fatima and Krammer, Florian and Sonda, Sabrina and Flanagan, Katie and Licciardi, Paul V. and Kent, Stephen J. and Rossjohn, Jamie and Thomas, Paul and Tosif, Shidan and Crawford, Nigel W. and van de Sandt, C. and Kedzierska, Katherine, SARS-CoV-2 Infection in Children Does Not Necessitate Establishment of Adaptive SARS- CoV-2-Specific Immunological Memory. Available at SSRN: https://ssrn.com/abstract=3956816 or http://dx.doi.org/10.2139/ssrn.3956816
This version of the paper has not been formally peer reviewed.

Louise C. Rowntree

University of Melbourne - Department of Microbiology and Immunology (DMI) ( email )

Melbourne, 3000
Australia

Thi H. O. Nguyen

University of Melbourne - Department of Microbiology and Immunology (DMI) ( email )

Melbourne, 3000
Australia

Lukasz Kedzierski

University of Melbourne - Department of Microbiology and Immunology (DMI) ( email )

Melbourne, 3000
Australia

Melanie R. Neeland

Murdoch Children's Research Institute - Infection and Immunity ( email )

Australia

Jan Petersen

Monash University - Infection and Immunity Program and Department of Biochemistry and Molecular Biology ( email )

23 Innovation Walk
Wellington Road
Clayton, 3800
Australia

Jeremy C. Crawford

St Jude Children’s Research Hospital - Department of Immunology ( email )

United States

Lilith F. Allen

University of Melbourne - Department of Microbiology and Immunology ( email )

185 Pelham Street
Carlton, 3053
Australia

Anastasia A. Minervina

St. Jude Children's Research Hospital - Department of Immunology ( email )

262 Danny Thomas Place
Memphis,, TN 38105
United States

Mikhail V. Pogorelyy

St. Jude Children's Research Hospital - Department of Immunology ( email )

262 Danny Thomas Place
Memphis,, TN 38105
United States

Priyanka Chaurasia

Monash University - Infection and Immunity Program ( email )

Australia

H T

University of Melbourne - Department of Microbiology and Immunology ( email )

Adam K. Wheatley

University of Melbourne - Department of Microbiology and Immunology (DMI) ( email )

Melbourne, 3000
Australia

Hayley A. McQuilten

University of Melbourne - Department of Microbiology and Immunology ( email )

185 Pelham Street
Carlton, 3053
Australia

E. Bridie Clemens

University of Melbourne - Department of Microbiology and Immunology (DMI) ( email )

Melbourne, 3000
Australia

Fatima Amanat

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Florian Krammer

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Sabrina Sonda

University of Tasmania - School of Medicine ( email )

French Street
Sandy Bay
Tasmania, 7250
Australia

Katie Flanagan

University of Tasmania - School of Health Sciences and School of Medicine

Paul V. Licciardi

Murdoch Children's Research Institute - Infection and Immunity ( email )

Australia

Stephen J. Kent

University of Melbourne - Department of Microbiology and Immunology ( email )

185 Pelham Street
Carlton, 3053
Australia

Jamie Rossjohn

Monash University - Infection and Immunity Program ( email )

Australia

Paul Thomas

St Jude Children’s Research Hospital - Department of Immunology ( email )

United States

Shidan Tosif

Murdoch Children's Research Institute - Infection and Immunity ( email )

Australia

Nigel W. Crawford

Murdoch Children's Research Institute ( email )

Murdoch Children's Research Institute - Infection and Immunity ( email )

Australia

C. Van de Sandt

University of Melbourne - Department of Microbiology and Immunology (DMI) ( email )

Melbourne, 3000
Australia

Katherine Kedzierska (Contact Author)

University of Melbourne - Department of Microbiology and Immunology (DMI)

Melbourne, 3000
Australia

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