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Background: According to Norwegian registries, 91% of individuals ≥ 16 years had received ≥ 1 dose of COVID-19 vaccine by mid-July 2022, whereas less than 2% of children < 12 years were vaccinated. Confirmed COVID-19 was reported for 27% of the population, but relaxation of testing lead to substantial underreporting. We have characterized the humoral immunity to SARS-CoV-2 in Norway in the late summer of 2022 by estimating the seroprevalence and identifying antibody profiles based on reactivity to Wuhan or Omicron-like viruses in a nationwide cross-sectional collection of residual sera, and validated our findings using cohort sera. Methods: 1,914 anonymized convenience sera and 243 NorFlu-cohort sera previously collected from the Oslo-area with reported infection and vaccination status were analyzed for antibodies against spike, the receptor-binding domain (RBD) of the ancestral Wuhan strain and Omicron BA.2 RBD, and nucleocapsid (N). Samples were also tested for antibodies inhibiting RBD-ACE2 interaction. Neutralization assays were performed on subsets of residual sera against B.1, BA.2, XBB.1.5 and BQ.1.1. Results: The national seroprevalence estimate from vaccination and/or infection was 99.1% (95% CrI 97.0-100.0%) based on Wuhan (spike_W and RBD_W) and RBD_BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD_BA2 than RBD_W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD_BA2 antibodies compared to Wuhan-antibodies alone. 50.3% (95% CI 45.0-55.5%) of residual sera from children and 38.1% (95% CI 36.0-40.4%) of all residual sera were positive for anti-N-antibodies. By combining measurements of binding- and ACE2-RBD-interaction-inhibiting antibodies, reactivity profiles indicative of infection and vaccination history were identified and validated using cohort sera. Residual sera with a profile indicative of hybrid immunity were able to neutralize newer Omicron variants XBB.1.5 and BQ.1.1. Conclusions: By late summer of 2022, most of the Norwegian population had antibodies to SARS-CoV-2, and almost all children had been infected. Antibody profiles indicated that children mostly had experienced a primary Omicron infection, while hybrid immunity was common among adults. The finding that sera displaying hybrid immunity could neutralize newer Omicron variants indicates that Wuhan-like priming of the immune response did not have a harmful imprinting effect and that infections induce cross-reacting antibodies against future variants. [ABSTRACT FROM AUTHOR]

New immune evasive variants of SARS‐CoV‐2 continue to emerge, potentially causing new waves of covid‐19 disease. Here, we evaluate levels of neutralizing antibodies against isolates of Omicron variants, including BQ.1.1 and XBB, in sera harvested 3–4 weeks after vaccination or breakthrough infections. In addition, we evaluate neutralizing antibodies in 32 sera from October 2022, to evaluate immunity in Norwegian donors prior to the winter season. Most serum samples harvested in October 2022 had low levels of neutralizing antibodies against BQ.1.1 and especially XBB, explaining why these variants and their descendants have dominated in Norway during the 2022 and 2023 winter season. [ABSTRACT FROM AUTHOR]