Length of hospital stay and risk of intensive care admission and in-hospital death among COVID-19 patients in Norway: a register-based cohort study comparing patients fully vaccinated with an mRNA vaccine to unvaccinated patients

Objectives We estimated the length of stay (LoS) in hospital and the intensive care unit (ICU) and risk of admission to ICU and in-hospital death among COVID-19 patients ≥18 years in Norway who had been fully vaccinated with an mRNA vaccine (at least two doses or one dose and previous SARS-CoV-2 infection), compared to unvaccinated patients. Methods Using national registry data, we analyzed SARS-CoV-2–positive patients hospitalized in Norway between 1 February and 30 November 2021, with COVID-19 as the main cause of hospitalization. We ran Cox proportional hazards models adjusting for vaccination status, age, sex, county of residence, regional health authority, date of admission, country of birth, virus variant, and underlying risk factors. Results We included 716 fully vaccinated patients (crude overall median LoS: 5.2 days; admitted to ICU: 103 (14%); in-hospital death: 86 (13%)) and 2487 unvaccinated patients (crude overall median LoS: 5.0 days; admitted to ICU: 480 (19%); in-hospital death: 102 (4%)). In adjusted models, fully vaccinated patients had a shorter overall LoS in hospital (adjusted log hazard ratios (aHR) for discharge: 1.61, 95% CI: 1.24–2.08), shorter LoS without ICU (aHR: 1.27, 95% CI: 1.07–1.52), and lower risk of ICU admission (aHR: 0.50, 95% CI: 0.37–0.69) compared to unvaccinated patients. We observed no difference in the LoS in ICU or in risk of in-hospital death between fully vaccinated and unvaccinated patients. Discussion Fully vaccinated patients hospitalized with COVID-19 in Norway have a shorter LoS and lower risk of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.publishedVersio

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

BACKGROUND: rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. METHODS: We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS: In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9-100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3-100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae. INTERPRETATION: The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters. FUNDING: WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development)

Modeling geographic vaccination strategies for COVID-19 in Norway.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic

Invasive meningococcal disease in Norway in the two decades before the COVID-19 pandemic

Objectives: Disease caused by the bacterium Neisseria meningitidis remains a worldwide public health challenge, despite the steadily decreasing incidence in Western countries. The objective of this study was to explore the epidemiology of invasive meningococcal disease in Norway over the last two decades. Design: All isolates sent to the National Reference Laboratory from patients with invasive meningococcal disease between the years 2000 and 2019 were analyzed using whole genome sequencing (total: 625). Results: A five-fold decrease in case numbers occurred over this period, and the situation has gone from being dominated by serogroup B to one where serogroups Y and W are more prevalent. Concurrently, the mean age at infection has increased from 18 to 33 years. Among the 350 serogroup B isolates, 87% were an exact match or cross-reactive with one or both the currently available serogroup B vaccines, but the proportion decreased in the past decade. Core genome analyses revealed a high variation in the number of allelic differences accumulated in epidemiologically linked isolates to the point that near-identical isolates were found several years apart. Conclusion: Allelic distance is an imprecise metric for the degree of epidemiologic linkage between isolates in N. meningitidis

Cost-effectiveness of meningococcal vaccination of Norwegian teenagers with a quadrivalent ACWY conjugate vaccine

n 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 hospita-lizations, 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

Cost-effectiveness of meningococcal vaccination of Norwegian teenagers with a quadrivalent ACWY conjugate vaccine

n 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 hospita-lizations, 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

Meningococcal carriage in Norwegian teenagers: strain characterisation and assessment of risk factors

Abstract Teenagers have a higher risk of invasive meningococcal disease (IMD) than the general population. This cross-sectional study aimed to characterise strains of Neisseria meningitidis circulating among Norwegian teenagers and to assess risk factors for meningococcal carriage. Oropharyngeal swabs were collected from secondary-school students in southeastern Norway in 2018–2019. Meningococcal isolates were characterised using whole genome sequencing. Risk factors for meningococcal carriage were assessed from questionnaire data. Samples were obtained from 2296 12–24-year-olds (majority 13–19-year-olds). N. meningitidis was identified in 167 (7.3%) individuals. The highest carriage rate was found among 18-year-olds (16.4%). Most carriage isolates were capsule null (40.1%) or genogroup Y (33.5%). Clonal complexes cc23 (35.9%) and cc198 (32.3%) dominated and 38.9% of carriage strains were similar to invasive strains currently causing IMD in Norway. Use of Swedish snus (smokeless tobacco) (OR 1.56, 95% CI 1.07–2.27), kissing >two persons/month (OR 2.76, 95% CI 1.49–5.10) and partying >10 times/3months (OR 3.50, 95% CI 1.45–8.48) were associated with carriage, while age, cigarette smoking, sharing of drinking bottles and meningococcal vaccination were not. The high meningococcal carriage rate among 18-year-olds is probably due to risk-related behaviour. Use of Swedish snus is possibly a new risk factor for meningococcal carriage. Almost 40% of circulating carriage strains have invasive potential

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ca Suffit!)

Background rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. Findings In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae

Meningococcal carriage in Norwegian teenagers: strain characterisation and assessment of risk factors

Abstract Teenagers have a higher risk of invasive meningococcal disease (IMD) than the general population. This cross-sectional study aimed to characterise strains of Neisseria meningitidis circulating among Norwegian teenagers and to assess risk factors for meningococcal carriage. Oropharyngeal swabs were collected from secondary-school students in southeastern Norway in 2018–2019. Meningococcal isolates were characterised using whole genome sequencing. Risk factors for meningococcal carriage were assessed from questionnaire data. Samples were obtained from 2296 12–24-year-olds (majority 13–19-year-olds). N. meningitidis was identified in 167 (7.3%) individuals. The highest carriage rate was found among 18-year-olds (16.4%). Most carriage isolates were capsule null (40.1%) or genogroup Y (33.5%). Clonal complexes cc23 (35.9%) and cc198 (32.3%) dominated and 38.9% of carriage strains were similar to invasive strains currently causing IMD in Norway. Use of Swedish snus (smokeless tobacco) (OR 1.56, 95% CI 1.07–2.27), kissing >two persons/month (OR 2.76, 95% CI 1.49–5.10) and partying >10 times/3months (OR 3.50, 95% CI 1.45–8.48) were associated with carriage, while age, cigarette smoking, sharing of drinking bottles and meningococcal vaccination were not. The high meningococcal carriage rate among 18-year-olds is probably due to risk-related behaviour. Use of Swedish snus is possibly a new risk factor for meningococcal carriage. Almost 40% of circulating carriage strains have invasive potential