Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity

Ntombi Benede; Marius B Tincho; Avril Walters; Vennesa Subbiah; Amkele Ngomti; Richard Baguma; Claire Butters; Lina Hahnle; Mathilda Mennen; Sango Skelem; Marguerite Adriaanse; Heidi Facey-Thomas; Christiaan Scott; Jonathan Day; Timothy F Spracklen; Strauss van Graan; Sashkia R Balla; Thandeka Moyo-Gwete; Penny L Moore; Rae MacGinty; Maresa Botha; Lesley Workman; Marina Johnson; David Goldblatt; Heather J Zar; Ntobeko A B Ntusi; Liesl Zühlke; Kate Webb; Catherine Riou; Wendy A Burgers; Roanne S Keeton

doi:10.1016/j.isci.2023.108728

Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity

iScience. 2023 Dec 14;27(1):108728. doi: 10.1016/j.isci.2023.108728. eCollection 2024 Jan 19.

Authors

Ntombi Benede^{1

2}, Marius B Tincho^{1

2}, Avril Walters^{1

2}, Vennesa Subbiah^{1

2}, Amkele Ngomti^{1

2}, Richard Baguma^{1

2}, Claire Butters³, Lina Hahnle⁴, Mathilda Mennen⁴, Sango Skelem⁴, Marguerite Adriaanse⁴, Heidi Facey-Thomas⁵, Christiaan Scott³, Jonathan Day³, Timothy F Spracklen^{5

6

7}, Strauss van Graan^{8

9}, Sashkia R Balla^{8

9}, Thandeka Moyo-Gwete^{8

9}, Penny L Moore^{1

8

9

10}, Rae MacGinty^{5

11}, Maresa Botha^{5

11}, Lesley Workman^{5

11}, Marina Johnson¹², David Goldblatt¹², Heather J Zar^{1

5

11

13}, Ntobeko A B Ntusi^{1

4

6

13}, Liesl Zühlke^{1

5

6

7}, Kate Webb^{3

14}, Catherine Riou^{1

2

13}, Wendy A Burgers^{1

2

13}, Roanne S Keeton^{1

2}

Affiliations

¹ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.
² Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory, South Africa.
³ Division of Paediatric Rheumatology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Observatory, South Africa.
⁴ Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory, South Africa.
⁵ Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
⁶ Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
⁷ South African Medical Research Council, Francie Van Zijl Drive, Parow Cape Town, South Africa.
⁸ National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
⁹ SA MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
¹¹ Medical Research Council (MRC) Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
¹² Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London, London, UK.
¹³ Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory, South Africa.
¹⁴ Crick African Network, The Francis Crick Institute, London, UK.

Abstract

SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on SARS-CoV-2 antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4⁺ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4⁺ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4⁺ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children.

Keywords: Components of the immune system; Immune response; Immunology; Virology.

Abstract

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