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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in children.

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

Background

Studies have reported that children have been less prone to infection by the SARS-CoV-2 Wuhan strain than adults. However, the emergence of mutant variants and higher vaccination rates in adults than children have resulted in 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 40.6% of children aged 5 – 11 were double vaccinated in Australia until August 2022. SARS-CoV-2 Omicron causes less severe disease than the Delta variant in children and adults.

Several reports suggest that adults mount a robust Omicron-specific humoral response, but there is a paucity of data in children. Previously, the authors reported that 37.6% of children infected with ancestral SARS-CoV-2 had seroconverted, compared to 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 present study evaluated seroconversion rates and antibody responses in Australian children during the three COVID-19 waves. Suspected COVID-19 cases and their household members were tested by reverse-transcription polymerase chain reaction (RT-PCR) or rapid antigen tests (RAT). Confirmed cases and household members participated in the household cohort study.

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

Around 580 children and adults were enrolled from March 2020 to July 2022. Non-vaccinated individuals aged 17 years or younger with a confirmed PCR or RAT result were included in the study. Additionally, partially vaccinated children who experienced a vaccine breakthrough infection were included.

Fifty-six children were infected with the SARS-CoV-2 Wuhan strain, and 21 (37.5%) were seroconverted by 36 days post-infection, whereas 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 a vaccine breakthrough Omicron infection showed > 61-fold increased IgG geometric mean concentration (GMC) than non-vaccinated Omicron-infected children. Similarly, reduced neutralizing responses with a Wuhan antigen-based sVNT were detected in non-vaccinated Omicron-infected children. Specifically, only one Omicron-infected pediatric case showed seroconversion had a positive neutralizing response.

In contrast, 19 of the 21 individuals who seroconverted after the Wuhan infection had a neutralizing response; all Delta-infected or breakthrough cases showed neutralizing antibody response. When variant-specific antigens were used for sVNT, Omicron-specific neutralizing responses were noted in nine children of the Omicron cohort, albeit the responses were significantly lower than 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 non-vaccinated Omicron-infected adults than children due to the high vaccination rate in adults.

Conclusions

The findings indicated that nearly all children attained seroconversion following infection with SARS-CoV-2 Omicron. Children mounted weaker antibody response to SARS-CoV-2 Wuhan or Delta, contrasting with observations in adults. Vaccinated children with a breakthrough infection had the highest antibody response against the Omicron variant.

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

In summary, the study observed that immune response against SARS-CoV-2 in children is variable. Although most non-vaccinated Delta- or Omicron-infected children seroconvert, the antibody responses against the Omicron variant were much weaker. This could increase reinfection risk with severe long-term implications for children’s health. Moreover, antibody responses in vaccinated children underscore the significance of vaccination for protective immunity.

*Important notice

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

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

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