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At the beginning of the SARS-COV-2 pandemic, limited information regarding disease burden, prevalence and immune response was available in the pediatric population. This thesis investigated SARS-CoV-2 specific IgG antibodies for the retrospective analysis of SARS-CoV-2 exposure in children. A sensitive and specific ELISA was developed to detect RBD-specific IgG antibodies in saliva. IgG antibodies diffuse from plasma into saliva, resulting in correlating IgG levels. Further, salivary antibodies are crucial for the immune response as they form the first line of defense against the SARS-CoV-2 virus. The saliva collection is simple and non-invasive, which makes it suitable for population-based studies, particularly for sample collections with children and adolescents.
After optimization, the ELISA assay displayed a high sensitivity (87%) with maximized specificity. This assay was implemented in a prospective, longitudinal, observational study (“Coro-Buddy”) measuring the seroprevalence of children and youths in Tübingen. Overall, 2069 children and adolescents were included and repeatedly sampled. In the first year of the pandemic in 2020, 837 children aged 1 to 10 years old were included in a substudy. The overall SARS-CoV-2 exposure in 2020 was comparably low at 1.6% but 3 times higher than the registered PCR positivity of 0.5% for the respective age group. This discrepancy might be linked to a widely used symptom-based test strategy. However, a distinct difference in prevalence was observed between preschool and primary school children of 0.4% and 3.0%, respectively. There is evidence that young children were less often infected with the SARS-CoV-2 wild-type variant than older population groups.
Additional experiments showed that mild SARS-CoV-2 wild-type infections in adults can induce a long-lasting antibody response that can persist over one year in plasma and saliva. However, antibodies waned over time, potentially lowering the protection against SARS-CoV-2 infection. A subsequent COVID-19 vaccination boosted IgG levels tremendously in both specimens and greatly enhanced neutralization activity compared to the non-vaccinated, convalescent cohort.
With the emergence of the Omicron variant in 2021, the progression of the pandemic changed, and the number of infected cases rose rapidly worldwide. Unexpectedly, a profound difference in the antibody expression between pre-Omicron and Omicron convalescent youths was found. Most children exposed to SARS-CoV-2 for the first time developed, after an Omicron infection, no RBD-specific IgG antibodies in saliva and plasma. A similar phenomenon was observed for other antigens (trimeric Spike and NCP). Altogether, there is strong evidence that the immune system was altered by the Omicron variant, leading to a reduced antibody response in youths. Potentially, this could lead to an increased risk of reinfection by newly emerging SARS-CoV-2 variants.
In summary, saliva-based ELISA has proven to be a powerful tool for investigating immune response and SARS-CoV-2 prevalence in a large study cohort. Regarding future applications, saliva-based assays can contribute much by examining the prevalence and immune response in population-based studies, especially considering new upcoming SARS-CoV-2 variants and other pandemics. |
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