Nationwide SARS-CoV-2 Seroprevalence Trends in the Netherlands in the Variant of Concern Era, 2021-2022: an Ongoing Prospective Cohort Study

ABSTRACT Background Repeated population-based SARS-CoV-2 serosurveillance is key in complementing other surveillance tools. Aim Assessing trends in infection- and/or vaccine-induced immunity, including breakthrough infections, among (sub)groups and regions in the Dutch population during the Variant of Concern (VOC)-era whilst varying levels of stringency, to evaluate population immunity dynamics and inform future pandemic response planning. Methods In this prospective population-based cohort, randomly-selected participants (n=9,985) aged 1-92 years (recruited since early-2020) donated home-collected fingerstick blood samples at six timepoints in 2021-2022, covering waves dominated by Alpha, Delta, and Omicron (BA.1, BA.2, BA.5). IgG antibody assessments against Spike-S1 and Nucleoprotein were combined with vaccination- and testing data to estimate infection-induced (inf) and total (infection- and vaccination-induced) seroprevalence. Results In 2021, nationwide inf-seroprevalence rose modestly from 12% since Alpha to 26% amidst Delta, while total seroprevalence increased rapidly to nearly 90%, particularly fast in vulnerable groups (i.e., elderly and those with comorbidities). Highest infection rates were noticeable in adolescents and young adults, low/middle educated elderly, non-Western, contact professions (other than healthcare), and low-vaccination coverage regions. In 2022, following Omicron emergence, inf-seroprevalence elevated sharply to 62% and further to 86%, with frequent breakthrough infections and reduction of seroprevalence dissimilarities between most groups. Whereas >90% of <60-year-olds had been infected, 30% of vaccinated vulnerable individuals had not acquired hybrid immunity. Conclusion Although total SARS-CoV-2 seroprevalence had increased rapidly, infection rates were unequally distributed within the Dutch population. Ongoing tailored vaccination efforts and (sero-)monitoring of vulnerable groups remain important given their lowest rate of hybrid immunity and highest susceptibility to severe disease.