Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023.

BACKGROUND: Non-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic. METHODS: To evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023. RESULTS: Influenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade. CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.

Frequency and risk of SARS-CoV-2 reinfections in Norway: a nation-wide study, February 2020 to January 2022.

BACKGROUND: SARS-CoV-2 reinfection rates have been shown to vary depending on the circulating variant, vaccination status and background immunity, as well as the time interval used to identify reinfections. This study describes the frequency of SARS-CoV-2 reinfections in Norway using different time intervals and assesses potential factors that could impact the risk of reinfections during the different variant waves. METHODS: We used linked individual-level data from national registries to conduct a retrospective cohort study including all cases with a positive test for SARS-CoV-2 from February 2020 to January 2022. Time intervals of 30, 60, 90 or 180 days between positive tests were used to define potential reinfections. A multivariable Cox regression model was used to assess the risk of reinfection in terms of variants adjusting for vaccination status, demographic factors, and underlying comorbidities. RESULTS: The reinfection rate varied between 0.2%, 0.6% and 5.9% during the Alpha, Delta and early Omicron waves, respectively. In the multivariable model, younger age groups were associated with a higher risk of reinfection compared to older age groups, whereas vaccination was associated with protection against reinfection. Moreover, the risk of reinfection followed a pattern similar to risk of first infection. Individuals infected early in the pandemic had higher risk of reinfection than individuals infected in more recent waves. CONCLUSIONS: Reinfections increased markedly during the Omicron wave. Younger individuals, and primary infections during earlier waves were associated with an increased reinfection risk compared to primary infections during more recent waves, whereas vaccination was a protective factor. Our results highlight the importance of age and post infection waning immunity and are relevant when evaluating vaccination polices.

Evaluation of the pilot wastewater surveillance for SARS-CoV-2 in Norway, June 2022 - March 2023.

BACKGROUND: During the COVID-19 pandemic, wastewater-based surveillance gained great international interest as an additional tool to monitor SARS-CoV-2. In autumn 2021, the Norwegian Institute of Public Health decided to pilot a national wastewater surveillance (WWS) system for SARS-CoV-2 and its variants between June 2022 and March 2023. We evaluated the system to assess if it met its objectives and its attribute-based performance. METHODS: We adapted the available guidelines for evaluation of surveillance systems. The evaluation was carried out as a descriptive analysis and consisted of the following three steps: (i) description of the WWS system, (ii) identification of users and stakeholders, and (iii) analysis of the system's attributes and performance including sensitivity, specificity, timeliness, usefulness, representativeness, simplicity, flexibility, stability, and communication. Cross-correlation analysis was performed to assess the system's ability to provide early warning signal of new wave of infections. RESULTS: The pilot WWS system was a national surveillance system using existing wastewater infrastructures from the largest Norwegian municipalities. We found that the system was sensitive, timely, useful, representative, simple, flexible, acceptable, and stable to follow the general trend of infection. Preliminary results indicate that the system could provide an early signal of changes in variant distribution. However, challenges may arise with: (i) specificity due to temporary fluctuations of RNA levels in wastewater, (ii) representativeness when downscaling, and (iii) flexibility and acceptability when upscaling the system due to limited resources and/or capacity. CONCLUSIONS: Our results showed that the pilot WWS system met most of its surveillance objectives. The system was able to provide an early warning signal of 1-2 weeks, and the system was useful to monitor infections at population level and complement routine surveillance when individual testing activity was low. However, temporary fluctuations of WWS values need to be carefully interpreted. To improve quality and efficiency, we recommend to standardise and validate methods for assessing trends of new waves of infection and variants, evaluate the WWS system using a longer operational period particularly for new variants, and conduct prevalence studies in the population to calibrate the system and improve data interpretation.

Poor neutralizing antibody responses against SARS-CoV-2 Omicron BQ.1.1 and XBB in Norway in October 2022.

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.

Effectiveness of BNT162b2 vaccine against SARS-CoV-2 Delta and Omicron infection in adolescents, Norway, August 2021 to January 2022.

OBJECTIVES: We estimated the BNT162b2 vaccine effectiveness (VE) against any (symptomatic or not) SARS-CoV-2 Delta and Omicron infection among adolescents (aged 12-17 years) in Norway from August 2021 to January 2022. METHODS: We used Cox proportional hazard models, where vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, residence county, birth country, and living conditions. RESULTS: The VE against Delta infection peaked at 68% (95% confidence interval [CI]: 64-71%) and 62% (95% CI: 57-66%) in days 21-48 after the first dose among those aged 12-15 years and 16-17 years, respectively. Among those aged 16-17 years who received two doses, the VE against Delta infection peaked at 93% (95% CI: 90-95%) in days 35-62 and decreased to 84% (95% CI: 76-89%) in ≥63 days after vaccination. We did not observe a protective effect against Omicron infection after receiving one dose. Among those aged 16-17 years, the VE against Omicron infection peaked at 53% (95% CI: 43-62%) in 7-34 days after the second dose and decreased to 23% (95% CI: 3-40%) in ≥63 days after vaccination. CONCLUSION: We found a reduced protection after two BNT162b2 vaccine doses against any Omicron infection compared to Delta. Effectiveness decreased with time from vaccination for both variants. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during the Omicron dominance.

Molecular Epidemiology of the Norwegian SARS-CoV-2 Delta Lineage AY.63.

Extensive genomic surveillance has given great insights into the evolution of the SARS-CoV-2 virus and emerging variants. During the summer months of 2021, Norway was dominated by the Pango lineage AY.63 which is a sub-lineage of the highly transmissible Delta variant. Strikingly, AY.63 did not spread in other countries to any significant extent. AY.63 carried a key mutation, A222V, in the spike protein, as well as the deletion of three residues in nsp1. Although these mutations are close to functionally important areas, we did not find any evidence that they induced higher fitness compared to other Delta lineages. This variant was introduced to Norway at a time when there were low levels of SARS-CoV-2 and contact-reducing measures were relaxed, which probably explains why the lineage rose so quickly. Furthermore, we found that the lack of imports of AY.63 from other countries probably led to the eventual demise of the lineage in Norway.

Milder disease trajectory among COVID-19 patients hospitalised with the SARS-CoV-2 Omicron variant compared with the Delta variant in Norway.

Using individual-level national registry data, we conducted a cohort study to estimate differences in the length of hospital stay, and risk of admission to an intensive care unit and in-hospital death among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, compared with patients infected with Delta variant in Norway. We included 409 (38%) patients infected with Omicron and 666 (62%) infected with Delta who were hospitalised with coronavirus disease 2019 (COVID-19) as the main cause of hospitalisation between 6 December 2021 and 6 February 2022. Omicron patients had a 48% lower risk of intensive care admission (adjusted hazard ratios (aHR): 0.52, 95% confidence interval (CI): 0.34-0.80) and a 56% lower risk of in-hospital death (aHR: 0.44, 95%CI: 0.24-0.79) compared with Delta patients. Omicron patients had a shorter length of stay (with or without ICU stay) compared with Delta patients in the age groups from 18 to 79 years and those who had at least completed their primary vaccination. This supports growing evidence of reduced disease severity among hospitalised Omicron patients compared with Delta patients.

Risk factors, immune response and whole-genome sequencing of SARS-CoV-2 in a cruise ship outbreak in Norway.

OBJECTIVE: To improve understanding of SARS-CoV-2-transmission and prevention measures on cruise ships, we investigated a Norwegian cruise ship outbreak from July to August 2020 using a multidisciplinary approach after a rapid outbreak response launched by local and national health authorities. METHODS: We conducted a cross-sectional study among crew members using epidemiologic data and results from SARS-CoV-2 polymerase chain reaction (PCR) of nasopharynx-oropharynx samples, antibody analyses of blood samples, and whole-genome sequencing. RESULTS: We included 114 multinational crew members (71% participation), median age 36 years, and 69% male. The attack rate was 33%; 32 of 37 outbreak cases were seropositive 5-10 days after PCR. One PCR-negative participant was seropositive, suggesting a previous infection. Network-analysis showed clusters based on common exposures, including embarkation date, nationality, sharing a cabin with an infected cabin-mate (adjusted odds ratio [AOR] 3.27; 95% confidence interval [CI] 0.97-11.07, p = 0.057), and specific workplaces (mechanical operations: 9.17 [1.82-45.78], catering: 6.11 [1.83-20.38]). Breaches in testing, quarantine, and isolation practices before/during expeditions were reported. Whole-genome sequencing revealed lineage B.1.36, previously identified in Asia. Despite extensive sequencing, the continued transmission of B.1.36 in Norway was not detected. CONCLUSIONS: Our findings confirm the high risk of SARS-CoV-2-transmission on cruise ships related to workplace and cabin type and show that continued community transmission after the outbreak could be stopped by implementing immediate infection control measures at the final destination.

Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 Omicron BA.1 variant compared with the Delta variant, Norway, December 2021 to January 2022.

We included 39,524 COVID-19 Omicron and 51,481 Delta cases reported in Norway from December 2021 to January 2022. We estimated a 73% reduced risk of hospitalisation (adjusted hazard ratio: 0.27; 95% confidence interval: 0.20-0.36) for Omicron compared with Delta. Compared with unvaccinated groups, Omicron cases who had completed primary two-dose vaccination 7-179 days before diagnosis had a lower reduced risk than Delta (66% vs 93%). People vaccinated with three doses had a similar risk reduction (86% vs 88%).

No difference in risk of hospitalization between reported cases of the SARS-CoV-2 Delta variant and Alpha variant in Norway.

OBJECTIVES: To estimate the risk of hospitalization among reported cases of the Delta variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with the Alpha variant in Norway, and the risk of hospitalization by vaccination status. METHODS: A cohort study was conducted on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. Adjusted risk ratios (aRR) with 95% confidence intervals (CI) were calculated using multi-variable log-binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities. RESULTS: In total, 7977 cases of the Delta variant and 12,078 cases of the Alpha variant were included in this study. Overall, 347 (1.7%) cases were hospitalized. The aRR of hospitalization for the Delta variant compared with the Alpha variant was 0.97 (95% CI 0.76-1.23). Partially vaccinated cases had a 72% reduced risk of hospitalization (95% CI 59-82%), and fully vaccinated cases had a 76% reduced risk of hospitalization (95% CI 61-85%) compared with unvaccinated cases. CONCLUSIONS: No difference was found between the risk of hospitalization for Delta cases and Alpha cases in Norway. The results of this study support the notion that partially and fully vaccinated cases are highly protected against hospitalization with coronavirus disease 2019.

Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021.

In late November 2021, an outbreak of Omicron SARS-CoV-2 following a Christmas party with 117 attendees was detected in Oslo, Norway. We observed an attack rate of 74% and most cases developed symptoms. As at 13 December, none have been hospitalised. Most participants were 30-50 years old. Ninety-six percent of them were fully vaccinated. These findings corroborate reports that the Omicron variant may be more transmissible, and that vaccination may be less effective in preventing infection compared with Delta.

Comprehensive Contact Tracing, Testing and Sequencing Show Limited Transmission of SARS-CoV-2 between Children in Schools in Norway, August 2020 to May 2021.

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in schools has been a topic of controversy. In this study among school contacts of SARS-CoV-2 positive children in 43 contact-investigations, we investigated SARS-CoV-2 transmission in Norway, August 2020-May 2021. All participants were tested twice within seven to ten days, using SARS-CoV-2 PCR on home-sampled saliva. Positive samples were whole genome sequenced. Among the 559 child contacts, eight tested positive (1.4%, 95% CI 0.62-2.80), with no significant difference between primary (1.0%, 95% CI 0.27-2.53) and secondary schools (2.6%, 95% CI 0.70-6.39), p = 0.229, nor by viral strain, non-Alpha (1.4%, 95% CI 0.50-2.94) and Alpha variant (B.1.1.7) (1.7%, 95% CI 0.21-5.99), p = 0.665. One adult contact (1/100) tested positive. In 34 index cases, we detected 13 different SARS-CoV-2 Pango lineage variants, with B.1.1.7 being most frequent. In the eight contact-investigations with SARS-CoV-2 positive contacts, four had the same sequence identity as the index, one had no relation, and three were inconclusive. With mitigation measures in place, the spread of SARS-CoV-2 from children in schools is limited. By excluding contact-investigations with adult cases known at the time of enrolment, our data provide a valid estimate on the role of children in the transmission of SARS-CoV-2 in schools.

The impact of global lineage dynamics, border restrictions, and emergence of the B.1.1.7 lineage on the SARS-CoV-2 epidemic in Norway.

As the COVID-19 pandemic swept through an immunologically naïve human population, academics and public health professionals scrambled to establish methods and platforms for genomic surveillance and data sharing. This offered a rare opportunity to study the ecology and evolution of SARS-CoV-2 over the course of the ongoing pandemic. Here, we use population genetic and phylogenetic methodology to characterize the population dynamics of SARS-CoV-2 and reconstruct patterns of virus introductions and local transmission in Norway against this backdrop. The analyses demonstrated that the epidemic in Norway was largely import driven and characterized by the repeated introduction, establishment, and suppression of new transmission lineages. This pattern changed with the arrival of the B.1.1.7 lineage, which was able to establish a stable presence concomitant with the imposition of severe border restrictions.

Increased risk of hospitalisation and intensive care admission associated with reported cases of SARS-CoV-2 variants B.1.1.7 and B.1.351 in Norway, December 2020 -May 2021.

INTRODUCTION: Since their emergence, SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.351 have spread worldwide. We estimated the risk of hospitalisation and admission to an intensive care unit (ICU) for infections with B.1.1.7 and B.1.351 in Norway, compared to infections with non-VOC. MATERIALS AND METHODS: Using linked individual-level data from national registries, we conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway diagnosed between 28 December 2020 and 2 May 2021. Variants were identified based on whole genome sequencing, partial sequencing by Sanger sequencing or PCR screening for selected targets. The outcome was hospitalisation or ICU admission. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression to examine the association between SARS-CoV-2 variants B.1.1.7 and B.1.351 with i) hospital admission and ii) ICU admission compared to non-VOC. RESULTS: We included 23,169 cases of B.1.1.7, 548 B.1.351 and 4,584 non-VOC. Overall, 1,017 cases were hospitalised (3.6%) and 206 admitted to ICU (0.7%). B.1.1.7 was associated with a 1.9-fold increased risk of hospitalisation (aRR 95%CI 1.6-2.3) and a 1.8-fold increased risk of ICU admission (aRR 95%CI 1.2-2.8) compared to non-VOC. Among hospitalised cases, no difference was found in the risk of ICU admission between B.1.1.7 and non-VOC. B.1.351 was associated with a 2.4-fold increased risk of hospitalisation (aRR 95%CI 1.7-3.3) and a 2.7-fold increased risk of ICU admission (aRR 95%CI 1.2-6.5) compared to non-VOC. DISCUSSION: Our findings add to the growing evidence of a higher risk of severe disease among persons infected with B.1.1.7 or B.1.351. This highlights the importance of prevention and control measures to reduce transmission of these VOC in society, particularly ongoing vaccination programmes, and preparedness plans for hospital surge capacity.

Vaccine effectiveness against infection with the Delta (B.1.617.2) variant, Norway, April to August 2021.

Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0-27.4) and 64.6% (95% CI: 60.6-68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4-58.3) and 84.4% (95%CI: 81.8-86.5) against the Alpha variant.

Abrupt termination of the 2019/20 influenza season following preventive measures against COVID-19 in Denmark, Norway and Sweden.

BackgroundIn mid-March 2020, a range of public health and social measures (PHSM) against the then new coronavirus disease (COVID-19) were implemented in Denmark, Norway and Sweden.AimWe analysed the development of influenza cases during the implementation of PHSM against SARS-CoV-2 in the Scandinavian countries.MethodBased on the established national laboratory surveillance of influenza, we compared the number of human influenza cases in the weeks immediately before and after the implementation of SARS-CoV-2 PHSM by country. The 2019/20 influenza season was compared with the five previous seasons.ResultsA dramatic reduction in influenza cases was seen in all three countries, with only a 3- to 6-week duration from the peak of weekly influenza cases until the percentage dropped below 1%. In contrast, in the previous nine influenza seasons, the decline from the seasonal peak to below 1% of influenza-positive samples took more than 10 weeks.ConclusionsThe PHSM against SARS-CoV-2 were followed by a dramatic reduction in influenza cases, indicating a wider public health effect of the implemented measures.

Diagnostic performance of a SARS-CoV-2 rapid antigen test in a large, Norwegian cohort.

BACKGROUND: Rapid antigen tests (RATs) may be included in national strategies for handling the SARS-CoV-2 pandemic, as they provide test results rapidly, are easily performed outside laboratories, and enable immediate contract tracing. However, before implementation further clinical evaluation of test sensitivity is warranted. OBJECTIVES: To examine the performance of Abbott's Panbio™ COVID-19 Ag Rapid Test Device for SARS-CoV-2 testing in a low to medium prevalence setting in Norway. STUDY DESIGN: A prospective study comparing the results of the Panbio RAT with PCR in 4857 parallel samples collected at a SARS-CoV-2 test station in Oslo, and from COVID-19 outbreaks in six Norwegian municipalities. RESULTS: A total of 4857 cases were included in the study; 3991 and 866 cases from the test station and the outbreak municipalities, respectively. The prevalence at the test station in Oslo was 6.3 %, and the overall sensitivity of the RAT was 74 %. Increased sensitivity was observed in patients who experienced symptoms (79 %) and when considering samples with viral loads above estimated level of infectivity (84 %), while it was lower in asymptomatic persons (55 %). In the outbreak municipalities, the overall prevalence was 6.9 %, and the total sensitivity of the RAT was 70 %. CONCLUSIONS: Our results indicate that the test correctly identified most infectious individuals. Nevertheless, the sensitivity is considerably lower than for PCR, and it is important that the limitations of the test are kept in mind in the follow-up of tested individuals.