Abstract
COVID-19 is caused by the SARS-CoV-2 virus. It was first discovered in December
2019. It remains a novel disease, and there is still limited knowledge, especially regarding
immunity to new strains of SARS-CoV-2. Novel SARS-CoV-2 variants continue to emerge and
spread within the population more than four years after their initial emergence. However,
the number of SARS-CoV-2 infections may be underestimated. This underreporting is likely
due to the widespread availability of rapid antigen tests, which enable self-testing during
symptomatic periods and reduce the number of hospital visits or RT-PCR (reverse
transcription polymerase chain reaction) confirmations recorded in public health statistics.
Moreover, omicron infections often result in mild or asymptomatic cases, further
contributing to underreporting. The detection of anti-nucleocapsid antibodies serves as a
retrospective marker of SARS-CoV-2 infection, whereas anti-receptor binding domain (RBD)
antibodies typically indicate infection, vaccination, or both. Therefore, assessing SARS-CoV-2
immunity is critical for accurately monitoring disease burden and providing insights into
population-level immunity.
Due to high global vaccine coverage and repeated waves of infection, population
immunity has increased over time, though its heterogeneity remains dynamic across different
age groups. Moreover, initial exposure to an early strain through vaccination or infection has
shaped immunity by tending to enhance immune responses to past exposures more than to
subsequent variant infections, a phenomenon known as immune imprinting. Additionally,
the immune response in children remains poorly understood. Meanwhile, older adults are at
a higher risk of severe COVID-19, often experiencing prolonged illness, critical complications,
and increased mortality. These factors raise important questions about the existing immunity
level in the population against recently circulating variants and whether children and adults
should receive updated COVID-19 booster doses.
Like other parts of the world, Thailand has experienced multiple waves of SARS-CoV-
2 variants. A previous study conducted between October 2022 and January 2023 reported
that 72.4% of the population had infection-induced seroprevalence, while 97.4% possessed
SARS-CoV-2 antibodies, suggesting prior infection, vaccination, or both. However,
seroprotection against currently circulating variants remains unclear. Therefore, an extensive
study of age-related immune responses in the post-COVID-19 pandemic era and their crossreactivity to recently circulating SARS-CoV-2 variants is needed.
To address these gaps, we conducted a population-based serosurvey four years after
the onset of the COVID-19 pandemic across twelve study sites in Thailand. This study aims
to evaluate age-specific SARS-CoV-2 seroprevalence, with a particular focus on children, and
to assess the impact of SARS-CoV-2 exposure and vaccination on neutralizing activity against
the wild-type (WT) and the recently circulating JN.1 variant across different age groups. We
hypothesize that all age groups have continued to experience SARS-CoV-2 exposure,
resulting in high seroprevalence across the population, and that differences in prior infection
and vaccination history may contribute to the heterogeneity of neutralizing activity against
the wild-type (WT) and JN.1 across age groups.
Unlike previous studies in Thailand, this study was conducted between May and
August 2024 and included samples from unvaccinated infants especially under the age of
five years, and elderly individuals to represent a broader age range. It provides insights into
age-related immunity patterns, cross-reactivity to currently circulating variants, and the
infection landscape following the later Omicron wave. These findings will guide public
health strategies in monitoring SARS-CoV-2 exposure, optimizing vaccination policies
including booster dose recommendations and age-specific vaccine updates, and prioritizing
vaccine distribution based on cost-effectiveness.
As SARS-CoV-2 variants continue to emerge, the extent of their impact on shaping
population immunity through repeated waves remains poorly understood. This study
assessed age-specific immune responses and the effects of vaccination on neutralization
against wild-type (WT) and JN.1 variants. We analyzed 4,371 serum samples from individuals
aged 6 months–80 years (May-August 2024). We found that 95.1% of participants had
detectable anti-N Ig, suggesting widespread prior infection. Among unvaccinated children (6
months–4 years), 96.5% exhibited anti-RBD or anti-N Ig antibodies mostly from asymptomatic
infections. Neutralization against JN.1 did not significantly differ by age, but children aged 6
months–4 years exhibited higher JN.1 neutralization than WT, while individuals aged ≥12
years showed the opposite pattern. Unvaccinated individuals demonstrated stronger
neutralization against JN.1, whereas vaccinated participants had lower neutralization against
JN.1 relative to WT, regardless of vaccine dose. No significant differences in JN.1
neutralization were observed across vaccine doses or age groups. Although 86.5% of
participants exhibited neutralizing activity against JN.1, the titers remained relatively low.
These findings highlight that almost all children experienced asymptomatic SARSCoV-2 infection and suggest that natural exposure maintains immunity in adults. Infectiondriven boosting may improve community-wide protection and alleviate immune imprinting,
offering key insights for optimizing vaccine strategies.
