Symptoms, SARS-CoV-2 Antibodies, and Neutralization Capacity in a Cross Sectional-Population of German Children

Abstract

Background: Children and youth are affected rather mildly in the acute phase of COVID-19 and thus, SARS-CoV-2 infection infection may easily be overlooked. In the light of current discussions on the vaccinations of children it seems necessary to better identify children who are immune against SARS-CoV-2 due to a previous infection and to better understand COVID-19 related immune reactions in children. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a) randomly, if they had an appointment for a regular health check-up or (b) if parents and children volunteered and actively wanted to participate in the study. Symptoms were recorded and two antibody tests were performed in parallel directed against S (in house test) and N (Roche Elecsys) viral proteins. In children with antibody response in either test, neutralization activity was determined. Results: We identified antibodies against SARS-CoV-2 in 162 of 2,832 eligible children (5.7%) between end of May and end of July 2020 in three, in part strongly affected regions of Bavaria in the first wave of the pandemic. Approximately 60% of antibody positive children (n = 97) showed high levels (>97th percentile) of antibodies against N-protein, and for the S-protein, similar results were found. Sufficient neutralizing activity was detected for only 135 antibody positive children (86%), irrespective of age and sex. Initial COVID-19 symptoms were unspecific in children except for the loss of smell and taste and unrelated to antibody responses or neutralization capacity. Approximately 30% of PCR positive children did not show seroconversion in our small subsample in which PCR tests were performed. Conclusions: Symptoms of SARS-CoV-2 infections are unspecific in children and antibody responses show a dichotomous structure with strong responses in many and no detectable antibodies in PCR positive children and missing neutralization activity in a relevant proportion of the young population.

Keywords: COVID-19; SARS-CoV-2; antibody; children; neutralizing.

Figure 1

Map of Bavaria with location of centers contributing to the survey (red dots) and COVID-19 prevalence until July 2020 (color coded by county). Number for overall, negatively and positively tested children are given in the circle chart.

Figure 2

Comparison between the N protein directed Elecsys Anti-SARS-CoV-2 assay (total Ig) and the S protein directed in-house SARS-CoV-2 assay detecting IgG (IgG) in the total study population (N = 2,832). Strong dotted lines represent the assay cutoff values, ±10% borderline intervals (gray areas). Signal-to-cutoff (S/Co) ratios are given for both assays.

Figure 3

N- and S-protein specific binding antibody titer and neutralization capacity analysis of in any test positive children (n = 161). (A) Distribution of N-specific antibody signal (Elecsys, S/Co). (B) Distribution of S_RBD-protein ELISA binding antibody titers (S/Co). (C) Distribution of Neutralization titers (IC50). (D) Correlation of N-specific antibody signal (Elecsys, S/Co) with S_RBD-protein ELISA binding antibody titers (S/Co). (E) Correlation of N-specific antibody signal (Elecsys, S/Co) with S_RBD-protein ELISA binding antibody titers (S/Co).