Comparison of seroconversion rates and antibody responses in children across the three SARS-CoV-2 waves in Melbourne, Australia

In a recent study posted to the medRxiv* preprint server, researchers evaluated antibody responses to variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children.

Study: Comparison of antibody responses to SARS-CoV-2 variants in Australian children. Image credit: maxbelchenko/Shutterstock

Background

Studies have shown that children are less susceptible to infection by the SARS-CoV-2 Wuhan strain than adults. However, the emergence of mutant variants and higher vaccination rates in adults than in children have led to an increased incidence of coronavirus disease 2019 (COVID-19) in the pediatric population.

Australia has witnessed three waves of SARS-CoV-2 infections, driven by the ancestral strain, Delta and Omicron variants. Estimates indicate that up to August 2022 in Australia, 40.6% of children aged 5-11 years had been double vaccinated. SARS-CoV-2 Omicron causes less severe disease in children and adults than the Delta variant.

Several reports suggest that adults exhibit a robust Omicron-specific humoral response, but there is a lack of data in children. Previously, the authors reported that 37.6% of children infected with ancestral SARS-CoV-2 had undergone seroconversion, compared with 76.2% of adults. As such, it remains to be investigated whether such a trend occurs in children after infection with Delta or Omicron variants.

The study and findings

The current study evaluated seroconversion rates and antibody responses in Australian children during the three COVID-19 waves. Suspected cases of COVID-19 and their family members were tested using reverse transcription polymerase chain reaction (RT-PCR) or rapid antigen testing (RAT). Confirmed cases and household members participated in the household cohort study.

The team collected blood samples one month after the confirmed PCR or RAT diagnosis. An internal SARS-CoV-2 S1 enzyme-linked immunosorbent assay (ELISA) and surrogate virus neutralization assays were performed to quantify immunoglobulin G (IgG) antibodies and neutralize the antibody response against ancestral and variant-specific S1 antigens.

Approximately 580 children and adults were enrolled from March 2020 to July 2022. Unvaccinated individuals 17 years of age or younger with a confirmed PCR or RAT result were included in the study. In addition, partially vaccinated children who had a breakthrough infection from the vaccine were included.

Fifty-six children were infected with the SARS-CoV-2 Wuhan strain and 21 (37.5%) were seroconverted 36 days post-infection, while all Delta-infected and 13 (81%) Omicron-infected children were seroconverted. The S1-specific IgG to Omicron infection was 7.7- and 9.4-fold lower than the Wuhan strain and Delta infection.

Children with breakthrough vaccine Omicron infection showed >61-fold increased IgG geometric mean concentration (GMC) than unvaccinated Omicron-infected children. Similarly, reduced neutralizing responses with a Wuhan antigen-based sVNT were detected in unvaccinated Omicron-infected children. Specifically, only one Omicron-infected pediatric case demonstrated that seroconversion had a positive neutralizing response.

In contrast, 19 out of 21 individuals who seroconverted after Wuhan infection had a neutralizing response; all Delta-infected or breakthrough cases showed a neutralizing antibody response. When variant-specific antigens were used for sVNT, Omicron-specific neutralizing responses were observed in nine children of the Omicron cohort, although the responses were significantly lower than in children in the vaccine breakthrough cohort.

Children infected with the ancestral strain or Omicron variant had significantly lower IgG levels than adults; however, there were fewer unvaccinated Omicron-infected adults than children because of the high vaccination coverage in adults.

conclusions

The findings indicated that almost all children achieved seroconversion after infection with SARS-CoV-2 Omicron. Children showed a weaker antibody response to SARS-CoV-2 Wuhan or Delta, in contrast to observations in adults. Vaccinated children with breakthrough infection had the highest antibody response to the Omicron variant.

The authors noted that antibody responses to the Omicron variant may be underestimated when assessed using Wuhan-based antigen(s), which could have significant implications for seroprevalence studies. Some of the limitations of the study are the small sample size and lack of data on the infecting strain and viral load.

In summary, the study found that the immune response to SARS-CoV-2 in children is variable. Although most unvaccinated Delta or Omicron infected children seroconvert, antibody responses against the Omicron variant were much weaker. This could increase the risk of reinfection, with serious long-term health implications for children. In addition, antibody responses in vaccinated children underscore the importance of vaccination for protective immunity.

*Important announcement

medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, that should guide clinical practice/health-related behavior or be treated as established information.

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