No association between disease severity and respiratory syncytial virus subtypes RSV-A and RSV-B in hospitalized young children in Norway.

OBJECTIVE: There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. METHODS: Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. RESULTS: Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. CONCLUSIONS: No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway.

Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: Results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 - December 2019.

BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.

Antibodies against Neisseria meningitidis serogroups A, C, W and Y in serum and saliva of Norwegian adolescents.

INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

The burden of hospital-attended influenza in Norwegian children.

Background: Norwegian health authorities do not recommend universal pediatric vaccination against seasonal influenza. We aimed to estimate the incidence of influenza by age and underlying medical conditions in hospitalized Norwegian children aged <18 years. Methods: Active surveillance for influenza in children <18 years was implemented in five hospitals during 2015-18. Children with respiratory symptoms and/or fever were prospectively enrolled and tested for influenza. Surveillance data were linked to health registry data to estimate the national burden of influenza in hospitals. Results: In 309 (10%) out of 3,010 hospital contacts, the child tested positive for influenza, corresponding to an average incidence of 0.96 hospital-attended influenza cases per 1,000 children <18 years of age. Children <1 year of age (3.8 per 1,000 children) and children with underlying medical conditions (17 per 1,000 children with bronchopulmonary dysplasia) had the highest average incidence. Among <1 year old children, 3% tested positive for influenza, compared to 25% for children aged 6-17. Few children were vaccinated against influenza. Conclusions: Children <1 year of age and children with underlying medical conditions had a higher incidence of influenza requiring hospital treatment compared to the general population. Effective interventions against seasonal influenza for children in Norway should be considered.

Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age.

Objective: To evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection. Study design: We prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015-2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data. Results: Risk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71-16.7)], having siblings [aOR: 1.65 (95% CI 1.05-2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35-4.24)]. The length of hospital stay >72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65-7.54)], having siblings [aOR: 1.45 (95% CI 1.01-2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31-3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support. Conclusion: In a large cohort of children <59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.

Long-term exposure to fine particle elemental components and mortality in Europe: Results from six European administrative cohorts within the ELAPSE project.

Evidence for the association between long-term exposure to ambient particulate matter components and mortality from natural causes is sparse and inconsistent. We evaluated this association in six large administrative cohorts in the framework of the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) project. We analyzed data from country-wide administrative cohorts in Norway, Denmark, the Netherlands, Belgium, Switzerland and in Rome (Italy). Annual 2010 mean concentrations of copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V) and zinc (Zn) in fine particulate matter (PM2.5) were estimated using 100 × 100 m Europe-wide hybrid land use regression models assigned to the participants' residential addresses. We applied cohort-specific Cox proportional hazard models controlling for area- and individual-level covariates to evaluate associations with natural mortality. Two pollutant models adjusting for PM2.5 total mass or nitrogen dioxide (NO2) were also applied. We pooled cohort-specific estimates using a random effects meta-analysis. We included almost 27 million participants contributing more than 240 million person-years. All components except Zn were significantly associated with natural mortality [pooled Hazard Ratios (HRs) (95% CI): 1.037 (1.014, 1.060) per 5 ng/m3 Cu; 1.069 (1.031, 1.108) per 100 ng/m3 Fe; 1.039 (1.018, 1.062) per 50 ng/m3 K; 1.024 (1.006, 1.043) per 1 ng/m3 Ni; 1.036 (1.016, 1.057) per 200 ng/m3 S; 1.152 (1.048, 1.266) per 100 ng/m3 Si; 1.020 (1.006, 1.034) per 2 ng/m3 V]. Only K and Si were robust to PM2.5 or NO2 adjustment [pooled HRs (95% CI) per 50 ng/m3 in K: 1.025 (1.008, 1.044), 1.020 (0.999, 1.042) and per 100 ng/m3 in Si: 1.121 (1.039, 1.209), 1.068 (1.022, 1.117) adjusted for PM2.5 and NO2 correspondingly]. Our findings indicate an association of natural mortality with most components, which was reduced after adjustment for PM2.5 and especially NO2.

The burden of respiratory syncytial virus in children under 5 years of age in Norway.

OBJECTIVES: To estimate age-specific incidence of medically attended respiratory syncytial virus (RSV) infections in hospitalised Norwegian children and describe disease epidemiology. METHODS: Active prospective hospital surveillance for RSV in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were enrolled based on respiratory symptoms regardless of fever. Surveillance data were linked to national registry data to estimate the clinical burden of RSV. RESULTS: Of the children enrolled, 1096 (40%) were infected with RSV. The highest incidence rates were found in children 1 month of age, with a peak incidence of 43 per 1000 during the 2016-2017 season. In comparison, children 24-59 months of age had an infection rate of 1.4 per 1000 during the same winter season. The peak season was during the 2016-2017 winter, with an incidence rate of 6.0 per 1000 children 0-59 months of age. In the study population a total of 168 (15%) of the infected children had pre-existing medical conditions predisposing for more severe disease. High infection rates were found in this population. CONCLUSIONS: Children with comorbidities showed high hospital contact rates, but the majority of children in need of medical attention associated with RSV infection were previously healthy.

Household Transmission of SARS-CoV-2: A Prospective Longitudinal Study Showing Higher Viral Load and Increased Transmissibility of the Alpha Variant Compared to Previous Strains.

We studied the secondary attack rate (SAR), risk factors, and precautionary practices of household transmission in a prospective, longitudinal study. We further compared transmission between the Alpha (B.1.1.7) variant and non-Variant of Concern (non-VOC) viruses. From May 2020 throughout April 2021, we recruited 70 confirmed COVID-19 cases with 146 household contacts. Participants donated biological samples eight times over 6 weeks and answered questionnaires. SARS-CoV-2 infection was detected by real-time RT-PCR. Whole genome sequencing and droplet digital PCR were used to establish virus variant and viral load. SARS-CoV-2 transmission occurred in 60% of the households, and the overall SAR for household contacts was 50%. The SAR was significantly higher for the Alpha variant (78%) compared with non-VOC viruses (43%) and was associated with a higher viral load. SAR was higher in household contacts aged ≥40 years (69%) than in younger contacts (40-47%), and for contacts of primary cases with loss of taste/smell. Children had lower viral loads and were more often asymptomatic than adults. Sleeping separately from the primary case reduced the risk of transmission. In conclusion, we found substantial household transmission, particularly for the Alpha variant. Precautionary practices seem to reduce SAR, but preventing household transmission may become difficult with more contagious variants, depending on vaccine use and effectiveness.

Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis.

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.