Palle Valentiner-Branth

Background: Respiratory syncytial virus (RSV) is a major cause of hospitalisation among young infants worldwide. Denmark implemented a national maternal RSV vaccination programme in October 2025. In this nationwide register-based cohort study we estimate the vaccine effectiveness against RSV hospitalisation among infants aged 0-6 months following the first maternal RSV vaccination programme and evaluate the population-level impact.Methods; We included all live births between November 1, 2025 to March 31, 2026 and compared rates of RSV-related hospitalisation occurring before May 1, 2026 among infants to vaccinated and unvaccinated mothers using Cox regression with calendar time as the underlying timescale adjusted for potential confounders. Population-level impact was estimated using Danish RSV surveillance data.Findings: Of the 22,593 infants included, 16,416 (72.7%) were born to vaccinated mothers. During the study, 66 and 104 infants were hospitalised for RSV in the vaccinated and unvaccinated group, respectively. The adjusted vaccine effectiveness against RSV hospitalisation was 77.9% (95% CI 69.5-84.0) overall, higher among infants aged 0-90 days (82.6%, 95% CI 74.9-88.0) than among infants aged 91-180 days (56.8%, 95% CI 18.4-77.2). The population impact analysis showed a 70.4% reduction in RSV hospitalisations among infants aged 0-90 days.Interpretation: Maternal RSV vaccination provided substantial protection against RSV hospitalisation, particularly during the first months of life. A considerable reduction in RSV hospitalisations was observed at the population level. These findings support national programmes as an effective strategy to reduce severe RSV burden in early infancy and highlight the importance of successful programme implementation and high maternal vaccination coverage for maximising population-level benefit.

BACKGROUND: Influenza infection is a recognised trigger of acute myocardial infarction (AMI) and stroke, but whether influenza vaccination modifies this risk remains unclear. AIM: We aimed to quantify the short-term cardiovascular risk after laboratory-confirmed influenza infection and assess whether vaccination attenuates it. METHODS: We conducted a nationwide self-controlled case series study using Danish health registries (2014–2025) and included individuals aged ≥ 40 years with a first-ever hospital admission for AMI or stroke within ± 365 days of a PCR-confirmed influenza infection. We defined days 1–7 after specimen date as the risk period and excluded a 14-day pre-exposure period to reduce reverse causality, where influenza testing might be prompted by cardiovascular disease symptoms. We linked testing, hospitalisation, vaccination and mortality data deterministically via unique personal identifiers. We estimated incidence rate ratios (IRRs) and 95% confidence intervals (CI) with conditional Poisson regression. RESULTS: Among 1,221 individuals with a first-ever AMI (n = 429; 35%) or stroke (n = 792; 65%), median age was 75 years (interquartile range: 66–82); 561 (46%) were female. After calendar-month adjustment, the IRR for cardiovascular events during the risk period was 3.5 (95% CI: 2.6–4.7), higher for AMI (IRR = 4.7; 95% CI: 3.1–7.4) than stroke (IRR = 2.9; 95% CI: 2.0–4.2). Prior influenza vaccination during the same influenza season, recorded in 610 (50%) episodes, reduced the excess risk of AMI or stroke associated with influenza infection (interaction p = 0.020). CONCLUSIONS: Influenza infection conferred a transiently increased risk of first-time AMI and stroke. Vaccination substantially attenuated this risk, supporting its role in preventing cardiovascular complications after breakthrough infection.

BACKGROUND: The COVID-19 pandemic underscored the need and value of a standardised and timely surveillance system for severe acute respiratory infections (SARI) to inform epidemic preparedness and response. AIM: We aimed to develop an automated SARI surveillance system using electronic health records retrieved from pre-existing national health registers in Denmark. METHODS: We used the Danish Civil Register, the Danish National Patient Register and the Danish Microbiology Database to set up the system. First, we determined a SARI case definition for surveillance, choosing among six different potentially usable combinations of ICD-10 diagnosis codes by exploring how each combination captured patient characteristics (age, hospital admission length, mortality, laboratory tests and seasonality). Second, using this case definition, we evaluated the surveillance system’s timeliness and completeness by comparing weekly data reported with a delay of 1, 8, 15, 22 and 29 days, respectively, against a complete set of data extracted after 120 days. RESULTS: The selected case definition combined ICD-10 codes for influenza (J09-J11), acute lower viral and bacterial respiratory tract infections and bronchiolitis (J12-J22) and COVID-19 (B342A and B972A). With regards to timeliness and completeness of this definition, weekly data reported with a delay of 8 days was 89–93% complete and showed very similar patterns in weekly changes in SARI cases as data reported after 120 days. CONCLUSION: Our SARI surveillance system detected fluctuations in weekly SARI cases in a consistent and timely manner. We recommend countries to explore using electronic health registers as a resource-efficient alternative to standard SARI sentinel surveillance.

Aims: Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE-FLU trial recently found two electronic behavioural nudging letter strategies – a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 –effective in increasing influenza vaccination in Denmark. The aims of this pre-specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off-target effects on guideline-directed medical therapy (GDMT) use. Methods and results: The nationwide NUDGE-FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022–2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE-FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain-framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain-framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use. Conclusions: Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain-framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed. Clinical Trial Registration: ClinicalTrials.gov NCT05542004.

The XBB.1.5 updated COVID-19 mRNA vaccines currently form part of the national immunisation programmes in many countries including Denmark. Here we present a cohort analysis with national electronic health registry data estimating the protection offered by the updated vaccines against hospital admission in October 2023. After adjustment in a Cox proportional hazards regression model for sex, age, residency region and comorbidities, those who had received the seasonal COVID-19 vaccine were much less likely to have been hospitalised for COVID-19 compared with those who had not received the vaccine (HR=0.247, 95% CI 0.157, 0.389), although a negative control outcome analysis indicated that the unvaccinated group had somewhat poorer health in general. Overall, our early results indicate a high level of protection from the XBB.1.5 vaccines.

Background The recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different vaccine types, which necessitates new knowledge on vaccine effectiveness (VE). In this study, we aimed to estimate the VE when combining the ChAdOx1 vaccine as the first dose and an mRNA vaccine as the second dose. Methods This nationwide population-based cohort study estimated VE against SARS-CoV-2 infection, all-cause and COVID-19 related hospitalization and death after receiving the ChAdOx1 vaccine as the first dose followed by an mRNA vaccine as the second dose. VE estimates were obtained using a Cox regression with calendar time as underlying time and adjusted for sex, age, comorbidity, heritage and hospital admission. Information on all individuals was extracted and linked from high-quality national registries. Results A total of 5,542,079 individuals were included in the analyses (97.6% of the total Danish population). A total of 144,360 were vaccinated with the ChAdOx1 vaccine as the first dose and of these 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 cases of SARS-CoV-2 infection were included. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% confidence interval (CI): 83; 92) 14 days after the second dose and onwards. There were no COVID-19 related hospitalizations and deaths among the individuals vaccinated with the combination of the ChAdOx1 and an mRNA vaccine during the study period. Conclusion In conclusion, this study found a reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals. This is similar to the VE of two doses of an mRNA vaccine. Longer follow-up time is needed to confirm vaccine induced protection against severe events, such as COVID-19 related hospitalization and death.

Background: Suspected adverse events (AE) after human papillomavirus (HPV) vaccines include postural orthostatic tachycardia syndrome (POTS), chronic fatigue syndrome (CFS), complex regional pain syndrome (CRPS) and symptoms including headache and orthostatic intolerance. Aim: We aimed to identify phenotypes of AEs after HPV vaccination, defined as patterns of AE terms (signs, symptoms, diagnoses), and to evaluate if identified phenotypes reflected previously suspected symptomatology or heightened public concerns over HPV vaccine safety since 1 January 2015. Methods: We conducted a retrospective observational study using latent class cluster analysis of all serious AE reports (n = 963) reported by females residing in Denmark between September 2009 and August 2017. Resulting clusters were characterised according to AE terms associated with POTS, CFS and CRPS before (September 2009–December 2014) and during (January 2015–August 2017) a time of heightened media activity regarding HPV vaccines. Results: Four clusters of AE reports were distinguished. The most common symptoms were fatigue, dizziness and headache but their frequency varied among clusters. The majority of reports in one cluster were submitted during a period of heightened media activity, including an anomalous spike in submissions in December 2015; a high proportion of these reports included the symptoms cognitive disorder (78%), abdominal pain (77%), dysuria (60%) and sleep disorder (60%). Conclusions: Non-specific symptoms including headache, fatigue and dizziness feature prominently in serious AE reports from females in Denmark. Our analysis identified a cluster of reports, likely media stimulated, with a focus on symptoms of CFS and POTS.

In recent years, human papillomavirus (HPV) vaccination of boys has been added to childhood vaccination programmes in several countries but, so far, no systematic population-based assessment with long-term follow-up has been undertaken of the relative incidence of adverse outcomes following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10–17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism. We conducted a national cohort study of 568 410 boys born in Denmark 1988–2006 and followed for 4 million person-years during 2006–16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status. Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10–17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI: 0.71–1.28, n = 46 cases in qHPV-vaccinated boys) and neurological diseases (RR = 0.67; 0.41–1.10, n = 16), as well as for venous thromboembolism (RR = 0.88; 0.33–2.35, n = 4). After taking multiple testing into account, none of the 52 individual outcomes studied appeared to occur in excess among qHPV-vaccinated boys. Although additional large-scale epidemiological studies are warranted, our findings provide population-based reassurance that qHPV vaccination of 10–17-year-old boys is unlikely to be associated with an elevated risk of autoimmune diseases, neurological diseases or venous thromboembolism.