Differential Adaptive Immune Responses Following SARS-CoV-2 Infection in Children Compared to Adults

Abstract

Background : SARS-CoV-2 infection elicits distinct clinical features in children and adults. Profiling the adaptive immune response following infection in children is essential to better understand and characterize these differences. Methods : Humoral and cell-mediated immune responses from unvaccinated pediatric and adult participants were analyzed following asymptomatic or mild non-Omicron SARS-CoV-2 infection. Levels of IgG and IgA targeting spike (S), receptor-binding domain (RBD), and nucleocapsid (N) proteins of SARS-CoV-2 were measured, while neutralizing antibody (nAb) titers were assessed against three viral strains (Wuhan, Omicron BA.1 and BA.4/BA.5). Specific T-cell memory responses were investigated by quantifying interferon-gamma secreting cells after stimulation with ancestral and variant strains of SARS-CoV-2, and seasonal human coronaviruses HCoV-OC43 and HCoV-HKU1. Results : The study comprised 28 children (3 to 17 [median=10] years old) and 28 adults (19 to 62 [median=42]). At a mean time of seven months (+/- 2.8 months) after SARS-CoV-2 infection, children and adults mounted comparable antibody levels against S and RBD, as well as similar neutralization capacity. However, children displayed a weaker cellular memory response to SARS-CoV-2 than adults, with a median of 88 [28-184] spot forming units per million of PBMCs in children compared to 208 [141-340] in adults (***, P < .001). In children, the level of IFN-gamma secreting cells in response to SARS-CoV-2 corresponds to that of seasonal coronaviruses. Conclusion : Long-term memory T-cell responses to SARS-CoV-2 are enhanced in adults compared to children who demonstrate equivalent responses to SARS-CoV-2 and other HCoV.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the CHAMO Innovation Fund (FPOC# CHA-21-010) and PSI Foundation (Grant # 21-22). The RECOVER study was supported by grants from the Canadian Institutes of Health Research VR2172712 (CQ, HD) and the Public Health Agency of Canada 2122-HQ-000225 (CQ, HD). CQ is supported through a Tier 1 Canada Research Chair in Infection Prevention (CRC-2019-00055). HD and SN are supported by the Fonds de Recherche du Quebec - Sante through a Senior Clinical Research Scholar award (HD) and a doctoral research scholarship (SN). HD is also supported by the Coalition for Epidemic Preparedness Innovations and Canadian Institutes of Health Research (CVL - 179495). The funders had no role in the study design, data collection or analysis, manuscript preparation or the decision to submit for publication.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Research Ethics Boards at the Children's Hospital of Eastern Ontario (CHEOREB#21/08X) and the Sainte-Justine University Hospital and Research Center (MP-21-2021-3035 and MP-21-2021-3046).

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Yes

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Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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