SARS-CoV-2 Seroprevalence Trends in the Netherlands in the Variant of Concern Era: Input for Future Response.

BACKGROUND: To inform future response planning we aimed to assess SARS-CoV-2 trends in infection- and/or vaccine-induced immunity, including breakthrough infections, among (sub)groups, professions and regions in the Dutch population during the Variant of Concern (VOC)-era. METHODS: In this prospective population-based cohort, randomly selected participants (n = 9985) aged 1-92 years (recruited early-2020) donated home-collected fingerstick-blood samples at six timepoints in 2021/2022, covering waves dominated by Alpha, Delta, and multiple Omicron (sub-)variants. IgG antibody assessment against Spike-S1 and Nucleoprotein was combined with vaccination- and testing data to estimate infection-induced (inf) and total (infection- and vaccination-induced) seroprevalence. RESULTS: Nationwide inf-seroprevalence rose modestly from 12% (95% CI 11-13) since Alpha to 26% (95% CI 24-28) amidst Delta, while total seroprevalence increased rapidly to 87% (95% CI 85-88), particularly in elderly and those with comorbidities (i.e., vulnerable groups). Interestingly, highest infection rates were noticeable among low/middle educated elderly, non-Western, those in contact professions, adolescents and young adults, and in low-vaccination coverage regions. Following Omicron emergence, inf-seroprevalence elevated sharply to 62% (95% CI 59-65) and further to 86% (95% CI 83-90) in late-2022, with frequent breakthrough infections and decreasing seroprevalence dissimilarities between most groups. Whereas > 90% of < 60-year-olds had been infected at least once, 30% of vaccinated vulnerable individuals had still not acquired hybrid immunity. CONCLUSIONS: Groups identified to have been infected disproportionally during the acute phase of the pandemic require specific attention in evaluation of control measures and future response planning worldwide. Furthermore, ongoing tailored vaccination efforts and (sero-)monitoring of vulnerable groups may remain important.

Serological profiling of pneumococcal proteins reveals unique patterns of acquisition, maintenance and waning of antibodies throughout life.

Streptococcus pneumoniae is a leading cause of morbidity and mortality in children and older adults. Yet knowledge on the development of pneumococcal protein-specific antibody responses throughout life is limited. To investigate this, we measured serum IgG levels to 55 pneumococcal proteins in 11-month old infants (n=73), 24-month old children (n=101), parents (n=99), adults without children <6 years of age (n= 99) and older adults aged >60 years (n=100). Our findings revealed low IgG levels in infancy, with distinct development patterns peaking in adults. A decrease in levels was observed for 27 antigens towards older age. Adults and older adults had increased IgG levels during pneumococcal carriage and at increased exposure risk to S. pneumoniae. Carriage was a stronger predictor than exposure or age for antibody responses. These findings highlight the dynamic nature of naturally acquired humoral immunity to pneumococcal proteins throughout life, offering insights for age-targeted interventions.

Impact of age on pneumococcal colonization of the nasopharynx and oral cavity: an ecological perspective.

Pneumococcal carriage studies have suggested that pneumococcal colonization in adults is largely limited to the oral cavity and oropharynx. In this study, we used total abundance-based ß-diversity (dissimilarity) and ß-diversity components to characterize age-related differences in pneumococcal serotype composition of respiratory samples. quantitative PCR (qPCR) was applied to detect pneumococcal serotypes in nasopharyngeal samples collected from 946 toddlers and 602 adults, saliva samples collected from a subset of 653 toddlers, and saliva and oropharyngeal samples collected from a subset of 318 adults. Bacterial culture rates from nasopharyngeal samples were used to characterize age-related differences in rates of colonizing bacteria. Dissimilarity in pneumococcal serotype composition was low among saliva and nasopharyngeal samples from children. In contrast, respiratory samples from adults exhibited high serotype dissimilarity, which predominantly consisted of abundance gradients and was associated with reduced nasopharyngeal colonization. Age-related serotype dissimilarity was high among nasopharyngeal samples and relatively low for saliva samples. Reduced nasopharyngeal colonization by pneumococcal serotypes coincided with significantly reduced Moraxella catarrhalis and Haemophilus influenzae and increased Staphylococcus aureus nasopharyngeal colonization rates among adults. Findings from this study suggest that within-host environmental conditions, utilized in the upper airways by pneumococcus and other bacteria, undergo age-related changes. It may result in a host-driven ecological succession of bacterial species colonizing the nasopharynx and lead to competitive exclusion of pneumococcus from the nasopharynx but not from the oral habitat. This explains the poor performance of nasopharyngeal samples for pneumococcal carriage among adults and indicates that in adults saliva more accurately represents the epidemiology of pneumococcal carriage than nasopharyngeal samples.

Contribution of SARS-CoV-2 infection preceding COVID-19 mRNA vaccination to generation of cellular and humoral immune responses in children.

Primary COVID-19 vaccination for children, 5-17 years of age, was offered in the Netherlands at a time when a substantial part of this population had already experienced a SARS-CoV-2 infection. While vaccination has been shown effective, underlying immune responses have not been extensively studied. We studied immune responsiveness to one and/or two doses of primary BNT162b2 mRNA vaccination and compared the humoral and cellular immune response in children with and without a preceding infection. Antibodies targeting the original SARS-CoV-2 Spike or Omicron Spike were measured by multiplex immunoassay. B-cell and T-cell responses were investigated using enzyme-linked immunosorbent spot (ELISpot) assays. The activation of CD4+ and CD8+ T cells was studied by flowcytometry. Primary vaccination induced both a humoral and cellular adaptive response in naive children. These responses were stronger in those with a history of infection prior to vaccination. A second vaccine dose did not further boost antibody levels in those who previously experienced an infection. Infection-induced responsiveness prior to vaccination was mainly detected in CD8+ T cells, while vaccine-induced T-cell responses were mostly by CD4+ T cells. Thus, SARS-CoV-2 infection prior to vaccination enhances adaptive cellular and humoral immune responses to primary COVID-19 vaccination in children. As most children are now expected to contract infection before the age of five, the impact of infection-induced immunity in children is of high relevance. Therefore, considering natural infection as a priming immunogen that enhances subsequent vaccine-responsiveness may help decision-making on the number and timing of vaccine doses.