Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study

Abstract

Background: Despite that pediatric COVID-19 is usually asymptomatic or mild, SARS-CoV-2 infection typically results in the development of an antibody response. Contradictory observations have been reported when the antibody response of children and adults were compared in terms of strength, specificity and perdurability.

Methods: This observational study includes three cohorts infected with SARS-CoV-2 between March 2020-July 2021: unvaccinated infected children (n=115), unvaccinated infected adults (n=62), and vaccinated infected children (n=76). Plasma anti-spike IgG antibodies and neutralising activity against Wuhan, Delta and Omicron variants after 7-17 months post-infection were analysed.

Findings: More than 95% of unvaccinated infected children and adults remained seropositive when evaluated at 382-491 and 386-420 days after infection, respectively. Anti-spike IgG titers and plasma neutralising activity against Wuhan, Delta and Omicron variants were higher in children compared to adults. No differences were found when unvaccinated infected children were stratified by age, gender or presence/absence of symptoms in the acute phase of SARS-CoV-2 infection, but a slight decrease in the antibody response was observed in those with comorbidities. Vaccination of previously infected children with two doses of the inactivated BBIBP-CorV or the mRNA vaccines, BNT162b2 and/or mRNA-1273, further increased anti-spike IgG titers and neutralising activity against Wuhan, Delta and Omicron variants.

Interpretation: Unvaccinated infected children mount a more potent and sustained antibody response compared with adults, which is significantly increased after vaccination. Further studies including not only the analysis of the immune response but also the effectiveness to prevent reinfections by the different Omicron lineages are required to optimise vaccination strategy in children.

Funding: National Agency for Scientific and Technological Promotion from Argentina (PICTO-COVID-SECUELAS-00007 and PMO-BID-PICT2018-2548).

Keywords: Antibodies; Pediatric COVID-19; SARS-CoV-2; Vaccines; Variants.

Figure 1

Persistence of the antibody response in unvaccinated infected children and adults. (a-c) Titres of IgG anti-spike antibodies defined by end point dilution in plasma from unvaccinated infected children (n=115) and unvaccinated infected adults (n=62). (a) Titres of IgG anti-spike antibodies plotted over days post infection (children, left panel; adults right panel). (b) Titres of IgG anti-spike antibodies in unvaccinated infected children grouped according days post infection (200 to 399 days, n=40) and 400 to 600 days (n=75). (c) Comparison of IgG anti-spike titres between unvaccinated infected children and unvaccinated infected adults. (d-e) Neutralisation activity against Wuhan, Delta and Omicron variants in plasma from unvaccinated infected children and unvaccinated infected adults. (d) Bar graphs showing the percentage of positive samples for neutralising activity against Wuhan, Delta and Omicron variants. (e) Neutralisation antibody titres against Wuhan, Delta and Omicron variants determined by the reciprocal IC50 in plasma from unvaccinated infected children and unvaccinated infected adults. (f) Comparison of neutralisation antibody titres against the three variants in paired samples. Fold decrease was calculated dividing the Wuhan IC50 by the Delta or Omicron IC50. (g) Representative curves of neutralising activity against Wuhan, Delta and Omicron variants in plasma from an unvaccinated infected child and an unvaccinated infected adult. These donors are shown in e and f as black filled dots. Dotted line indicates the limit of detection value. Median and min to max of n donors are shown in b, c and e. P values were determined by Pearson's Chi square test and Mann–Whitney U test: ** p<0.01, *** p<0.001, **** p<0.0001. Unvaccinated infected children (red circle), unvaccinated infected adults (blue circle).

Figure 2

Antibody response against Wuhan, Delta and Omicron variants in unvaccinated and vaccinated previously SARS-CoV-2 infected children. (a) Titres of IgG anti-spike antibodies defined by end point dilution in plasma from unvaccinated infected children (n=115) and infected children receiving one- (n=17) or two-doses of BBIBP-CorV (n=19) or one- (n=13) or two-doses (n=27) of mRNA vaccines. (b-c) Neutralising activity against Wuhan, Delta and Omicron variants in plasma from unvaccinated infected and vaccinated previously infected children with one-dose of BBIBP-CorV or mRNA vaccines (BNT162b2 / mRNA-1273). (b) Bar graphs show the percentage of positive samples for neutralising activity against Wuhan, Delta and Omicron variants. (c) Neutralisation antibody titres against Wuhan, Delta and Omicron variants determined by the reciprocal IC50 in plasma from unvaccinated infected and one-dose vaccinated previously infected children. (d-e) Neutralising activity against Wuhan, Delta and Omicron variants in plasma from unvaccinated infected and previously infected children vaccinated with two-doses of BBIBP-CorV or mRNA vaccines. (d) Bar graphs show the percentage of positive samples for neutralising activity against Wuhan, Delta and Omicron variants. (e) Neutralisation antibody titres against Wuhan, Delta and Omicron variants determined by the reciprocal IC50 in plasma from unvaccinated infected and two-doses vaccinated infected children. (f) Comparison of neutralisation antibody titres against the three variants in paired samples. Fold decrease was calculated dividing the Wuhan IC50 by the Delta or Omicron IC50. Dotted line indicates the limit of detection value. Median and min to max of n donors are shown in a, c and e. P values were determined by Pearson's Chi square test and Mann-Whitney U test: * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Unvaccinated infected children (red circle), one-dose vaccinated infected children (black circle), two-doses vaccinated infected children (filled black circle).