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Background: One year into the COVID‐19 pandemic, the cumulative number of confirmed COVID‐19 cases in Norway was still low. In January 2021, when the Norwegian COVID‐19 vaccination campaign started, the national seroprevalence estimate of SARS‐CoV‐2 antibodies was 3.2%. We have conducted a nationwide cross‐sectional study in August 2021 to investigate the overall prevalence of SARS‐CoV‐2 antibodies in Norway after 8 months of COVID‐19 mass vaccination and a third wave of SARS‐CoV‐2 infection. Methods: Residual sera were collected from laboratories across Norway in August 2021. In IgG antibodies against the spike protein, the spike receptor binding domain (RBD) and the nucleocapsid protein of SARS‐CoV‐2 were measured by a bead‐based flow cytometric assay. Results: In total, 1926 residual sera were collected from individuals aged 0–98 years; 55.1% were from women. The overall national estimated seroprevalence from vaccination and/or infection was 62.6% (credible interval [CrI] 60.1%–65.2%) based on having antibodies against both spike and RBD. Estimated seroprevalence increased with age. Among all samples, 11.7% had antibodies against nucleocapsid. For unvaccinated children <12 years, the seroprevalence estimate due to SARS‐CoV‐2 infection was 12.5% (95% CrI 9.3%–16.1%). Of seropositive samples from the unvaccinated children, 31.9% lacked anti‐nucleocapsid antibodies. Conclusions: The high overall SARS‐CoV‐2 seroprevalence estimates are in line with Norwegian registry data. Vaccination, not infection, contributed the most to the high seroprevalence in August 2021. Lack of antibodies against nucleocapsid should not automatically be interpreted as absence of previous infection as this could lead to underestimation of COVID‐19 cases in seroprevalence studies. [ABSTRACT FROM AUTHOR]

Seasonal influenza causes substantial numbers of hospitalizations annually. We have characterized the clinical picture and treatment practice in hospitalized adult influenza patients and assessed whether clinical risk scores on admission or influenza type were associated with severe outcomes. Clinical characteristics and risk scores on admission (CRB65, CRB, SIRS and quick Sequential Organ Failure Assessment [qSOFA]), treatment and severe outcomes (defined as: stay in intensive care unit (ICU), receiving oxygen supplementation or staying ≥5 days in hospital), were recorded in patients hospitalized with influenza at Oslo University Hospital, Norway, between 2014 and 2018. Among the 156 included patients, 52.6% had influenza A(H3N2), 32.6% influenza B and 12.8% influenza A(H1N1). Median age was 70 years and 59.6% of patients were ≥65 years. Nine (5.8%) of the patients were treated in ICU, 43.0% received oxygen and 47.4% stayed ≥5 days in hospital. Overall, 34.6% of the patients had a high CRB score on admission which was associated with stay in ICU and oxygen supplementation. Multivariate analyses identified age, and pneumonia (46.8%), but not influenza type, to be associated with severe outcomes. Antiviral treatment was given to 37.2% of the patients, while 77.6% received antibiotics. Only 25.5% of patients with influenza B received antiviral therapy. The influenza patients were mostly elderly, and few patients were treated in ICU. A high CRB score was associated with severe outcomes with possible implications for patient monitoring. Less than 40% of the patients received antiviral therapy, whereas the majority were treated with antibiotics, indicating potential for optimising treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Infection with the novel coronavirus SARS‐CoV‐2 induces antibodies that can be used as a proxy for COVID‐19. We present a repeated nationwide cross‐sectional study assessing the seroprevalence of SARS‐CoV‐2, the infection fatality rate (IFR), and infection hospitalization rate (IHR) during the first year of the pandemic in Norway. Methods: Residual serum samples were solicited in April/May 2020 (Round 1), in July/August 2020 (Round 2) and in January 2021 (Round 3). Antibodies against SARS‐CoV‐2 were measured using a flow cytometer‐based assay. Aggregate data on confirmed cases, COVID‐19‐associated deaths and hospitalizations were obtained from the Emergency preparedness registry for COVID‐19 (Beredt C19), and the seroprevalence estimates were used to estimate IFR and IHR. Results: Antibodies against SARS‐CoV‐2 were measured in 4840 samples. The estimated seroprevalence increased from 0.8% (95% credible interval [CrI] 0.4%–1.3%) after the first wave of the pandemic (Rounds 1 and 2 combined) to 3.2% (95% CrI 2.3%–4.2%) (Round 3). The IFR and IHR were higher in the first wave than in the second wave and increased with age. The IFR was 0.2% (95% CrI 0.1%–0.3%), and IHR was 0.9% (95% CrI 0.6%–1.5%) for the second wave. Conclusions: The seroprevalence estimates show a cumulative increase of SARS‐CoV‐2 infections over time in the Norwegian population and suggest some under‐recording of confirmed cases. The IFR and IHR were low, corresponding to the relatively low number of COVID‐19‐associated deaths and hospitalizations in Norway. Most of the Norwegian population was still susceptible to SARS‐CoV‐2 infection after the first year of the pandemic. [ABSTRACT FROM AUTHOR]

The incidence of invasive meningococcal disease (IMD) among Norwegian 16–19-year-olds was 1–7/100,000 in the decade before the COVID-19 pandemic, with serogroup Y (MenY) dominance. In contrast to many other European countries, meningococcal vaccines are not part of the national immunisation program (NIP) in Norway. This cross-sectional study aimed to measure the degree of natural immunity against Neisseria meningitidis among adolescents in Norway to evaluate the need for introducing tetravalent meningococcal conjugate vaccine (MCV4) in the NIP. Serum and saliva samples were collected from students in upper and lower secondary schools in Norway in 2018. Samples were analysed for meningococcal capsular polysaccharide (PS)-specific antibodies using a bead-based multiplex immunoassay. PS-specific antibody levels were linked to data on meningococcal carriage, vaccination status and risk factors for carriage (assessed with questionnaire) and analysed by linear regression of log transformed concentrations. A subset of samples from unvaccinated individuals was analysed for serum bactericidal antibodies (SBA). A total of 1344 participants, median age 16 years (range 12–24), were included in the study. Overall, 60.9% of the participants were female and 1137 (84.6%) were not vaccinated with MCV4. PS-specific antibody concentrations in serum and saliva were low among unvaccinated individuals for all serogroups and only 6.7–20.0% of the subpopulation with high PS-specific antibodies assessed with SBA had protective levels. Unvaccinated MenY carriers had higher levels of MenY anti-PS IgG in serum and IgA in saliva than those not carrying MenY. Use of Swedish snus was associated with lower anti-PS IgG levels in serum and waterpipe use with lower anti-PS IgG levels in saliva. Unvaccinated adolescents in Norway have a low degree of natural immunity against the serogroups of N. meningitidis predominating among cases of IMD in this age group. Therefore, introduction of MCV4 for adolescents in the NIP is recommended. [ABSTRACT FROM AUTHOR]

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&#95;W and RBD&#95;W) and RBD&#95;BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD&#95;BA2 than RBD&#95;W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD&#95;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., (© 2024. The Author(s).)

In Norway, the incidence of invasive meningococcal disease (IMD) is higher among 16-19-year-olds than in the general population. Most IMD cases among teenagers are caused by serogroup Y. Since 2011, one dose of meningococcal ACWY conjugate vaccine (MCV4) has been recommended for teenagers with out-of-pocket payment. The teenagers are usually vaccinated through the school health service at age 18. This study aimed to estimate costs and health gains of introducing MCV4 to Norwegian teenagers through the national immunization program (NIP). A Markov model was used to analyze the cost-effectiveness of universal MCV4 vaccination of either 15-year-olds or 18-years-olds. Occurrences of IMD were simulated from 15 until 23 years of age. Costs were estimated from a healthcare perspective. Sensitivity analyses evaluated the impact of vaccine price, vaccination uptake, IMD incidence and discount rate. Compared to today's practice of vaccinating 18-year-olds with out-of-pocket payment, introducing MCV4 to 15-year-olds in a NIP-setting, with 90% vaccine uptake and 50% rebate on vaccine price, prevented 3.2 hospitalizations, 0.20 sequelae and 0.47 deaths among 15-23-year-olds, annually. Total costs were reduced by €30,000 and 9.7 quality-adjusted life-years (QALYs) were gained per birth cohort. The probability of cost-effectiveness was 99.0%, assuming a willingness-to-pay threshold of €86,000/QALY for severe diseases in Norway. Cost-effectiveness was highly dependent on vaccine price. Vaccination of 18-year-olds in a NIP-setting was also cost-effective, but less than NIP-vaccination of 15-year-olds. Introduction of MCV4 to the 15-year-olds in the Norwegian NIP is likely to be cost-effective given a rebate on the vaccine price.

Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza.