Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity

Ntombi S B Benede; Marius B Tincho; Avril Walters; Vennesa Subbiah; Amkele Ngomti; Richard Baguma; Claire Butters; Mathilda Mennen; Sango Skelem; Marguerite Adriaanse; Strauss van Graan; Sashkia R Balla; Thandeka Moyo-Gwete; Penny L Moore; Maresa Botha; Lesley Workman; Heather J Zar; Ntobeko A B Ntusi; Liesl Zühlke; Kate Webb; Catherine Riou; Wendy A Burgers; Roanne S Keeton

doi:10.1101/2023.05.16.23290059

Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity

medRxiv [Preprint]. 2023 May 23:2023.05.16.23290059. doi: 10.1101/2023.05.16.23290059.

Authors

Ntombi S B 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 Butters¹, Mathilda Mennen³, Sango Skelem³, Marguerite Adriaanse³, Strauss van Graan^{4

5}, Sashkia R Balla^{4

5}, Thandeka Moyo-Gwete^{4

5}, Penny L Moore^{1

4

5

6}, Maresa Botha^{7

8}, Lesley Workman^{7

8}, Heather J Zar^{1

7

8

9}, Ntobeko A B Ntusi^{1

3

9

10}, Liesl Zühlke^{1

7

10

11}, Kate Webb^{11

12}, Catherine Riou^{1

2

9}, Wendy A Burgers^{1

2

9}, 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 Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory, South Africa.
⁴ National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
⁵ MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
⁶ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
⁷ Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
⁸ Medical Research Council (MRC) Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
⁹ Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory, South Africa.
¹⁰ Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
¹¹ South African Medical Research Council, Francie Van Zijl Drive, Parow Cape Town, South Africa.
¹² Crick African Network, The Francis Crick Institute, London, United Kingdom.

Abstract

SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on 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: Children; IgG responses; Polyfunctional profile; SARS-CoV-2; T cell response; endemic HCoV.

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Preprint

Abstract

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