Pediatric humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and two-dose vaccination during SARS-CoV-2 omicron BA.5 and BN.1 variants predominance in South Korea

Abstract

Background: Humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination during the Omicron BA.5 and BN.1 variants predominant period remains unexplored in pediatric population.

Methods: We examined anti-spike (anti-S) immunoglobulin G (IgG) responses in a total of 986 children aged 4-18 years who visited outpatient clinics between June 2022 and January 2023, with a history of SARS-CoV-2 infection alone, completed two doses of COVID-19 vaccination alone, vaccine-breakthrough infection (i.e., infection after the single dose of vaccination), and no antigenic exposure. Furthermore, to determine SARS-CoV-2 infection risk, the incidence of newly developed SARS-CoV-2 infection was investigated up to March 2023.

Results: The anti-S IgG levels in the 'vaccine-breakthrough infection' group exceeded those in the 'infection alone' and 'vaccination alone' groups (both P <0.01). Furthermore, the 'vaccination alone' group experienced more rapid anti-S IgG waning than the 'infection alone' and 'vaccine-breakthrough infection' groups (both P <0.01). We could not identify newly developed SARS-CoV-2 infection in the 'vaccine-breakthrough infection' group.

Conclusion: Our findings suggest that hybrid immunity, acquired from SARS-CoV-2 infection and COVID-19 vaccination, was a potentially higher and longer-lasting humoral immune response and protected against SARS-CoV-2 infection in pediatric population during Omicron BA.5 and BN.1 variants predominant.

Keywords: COVID-19; SARS-CoV-2; antibody response; child; hybrid immunity; vaccine.

Figure 1

Temporal kinetics of anti-SARS-CoV-2 spike protein (anti-S) IgG by different types of antigenic exposures by time since SARS-CoV-2 infection or COVID-19 vaccination. Dots represent anti-S IgG values induced by (A) SARS-CoV-2 infection alone, (B) COVID-19 vaccination alone, and (C) vaccine breakthrough infection. The thick curve indicates the trend in anti-Spike IgG using smoothing splines with a 95% confidence interval (shaded area).

Figure 2

Unadjusted comparison of anti-S IgG by category of SARS-CoV-2 infection and/or COVID-19 vaccination. P-values determined using the Kruskal-Wallis test. The comparisons do not adjust for sampling time, which is different for every group. The box plots denote median, the 25th percentile, and the 75th percentile of the anti-S (y-axis) and each group (x-axis) representing SARS-CoV-2 infection alone (light yellow), vaccination alone (light green), and vaccine breakthrough infection (pink).

Figure 3

Temporal kinetics of anti-SARS-CoV-2 nucleocapsid (anti-N) IgG in SARS-CoV-2 infected groups (n=536) and comparison of anti-N IgG by different age groups. Dots represent an individual sample, and horizontal lines in the box indicate the median value with the interquartile range with (A) time in months from infection to collect samples and (B) different age groups. P- values were determined using the Kruskal-Wallis test. Abbreviation: COI, cut-off index.