Background: Individuals with comorbidities are at increased risk of severe respiratory syncytial virus (RSV) infection. We estimated RSV-associated respiratory hospitalization among adults aged ≥45 years with comorbidities in Denmark and Scotland. Methods: By analyzing national hospital and virologic data, we estimated annual RSV-associated hospitalizations by 7 selected comorbidities and ages between 2010 and 2018. We estimated rate ratios of RSV-associated hospitalization for adults with comorbidity than the overall population. Results: In Denmark, annual RSV–associated hospitalization rates per 1000 adults ranged from 3.1 for asthma to 19.4 for chronic kidney disease (CKD). In Scotland, rates ranged from 2.4 for chronic liver disease to 9.0 for chronic obstructive pulmonary disease (COPD). In both countries, we found a 2- to 4-fold increased risk of RSV hospitalization for adults with COPD, ischemic heart disease, stroke, and diabetes; a 1.5- to 3-fold increased risk for asthma; and a 3- to 7-fold increased risk for CKD. RSV hospitalization rates among adults aged 45 to 64 years with COPD, asthma, ischemic heart disease, or CKD were higher than the overall population. Conclusions: This study provides important evidence for identifying risk groups and assisting health authorities in RSV vaccination policy making.

Background: Low awareness and lack of routine testing for respiratory syncytial virus (RSV) infections among adults has led to underreporting in hospital records. This study aimed to assess the underreporting and misclassification of RSV infections among adults hospitalized with an respiratory tract infection (RTI)-coded hospitalization. Methods: This study is an observational cohort study of RSV-associated hospitalizations among Danish adults (≥18 years old) conducted, between 2015 to 2018. Data were extracted from the Danish National Patient Registry (DNPR) and the Danish Microbiology Database. We identified RSV-positive hospitalizations by linking RTI-coded hospitalizations with a positive RSV test. Results: Using hospital admission registries, we identified 440 RSV-coded hospitalizations, of whom 420 (95%) had a positive RSV test registered. By linking patients with RTI-coded hospital admissions to RSV test result, we found 570 additional episodes of RSV-positive hospitalizations without an RSV-coded diagnosis. Conclusions: Our study of national register data showed that RSV is underreported among Danish adults. The study showed that the reliability of hospitalization data to estimate the burden of RSV among adults is questionable and are sensitive to changes in practice over time, even with complete nationwide healthcare data. Healthcare data can be useful to observe seasonality but to estimate the disease burden, prospective surveillance is recommended.

Respiratory syncytial virus (RSV) and influenza cause significant health challenges, particularly for individuals with comorbid conditions and older adults. However, information on the clinical manifestations and outcomes of adults hospitalized with RSV in Europe remains limited. This multicenter observational cohort study of adults hospitalized with RSV or influenza A or B from March 2016 to April 2020 investigated the clinical manifestations, mortality risk factors, and association with 90-day mortality rates by logistic regression analysis after adjustment for covariates. Of 988 patients hospitalized with either virus, 353 had RSV, 347 had influenza A, and 288 had influenza B infection. Patients with RSV, compared with those with influenza A or B, were more likely to have comorbid conditions (83% for RSV vs 72% for influenza A [P = .03] and 74% for influenza B [P = .001]) or pneumonia (41% vs 29% [P = .03] and 24% [P < .001], respectively). After adjustment for covariates, RSV infection was associated with an increased all-cause mortality rate within 90 days compared with influenza B (odds ratio, 2.16 [95% confidence interval, 1.20–3.87]; P = .01) but not influenza A (1.38 [.84–2.29]; P = .21). Increasing age and present pneumonia were identified as independent mortality risk factors in patients with RSV. Older adults hospitalized with RSV infections are at a higher risk of dying within 90 days of hospitalization than patients admitted with influenza B but at a similar risk as those admitted with influenza A, emphasizing the detrimental effects and severity of older patients being infected with RSV. Our findings underscore the need for strategic testing and vaccination approaches to mitigate the impact of RSV among older adults.

Background: Worldwide, respiratory syncytial virus (RSV) infections are among the most common causes of infant hospitalization. Host genetic factors influencing the risk and severity of RSV infection are not well known. Methods: We conducted a genome-wide association study (GWAS) to investigate single-nucleotide polymorphisms (SNPs) associated with severe RSV infections using a nested case-control design based on 2 Danish cohorts. We compared SNPs from 1786 children hospitalized with RSV to 45 060 controls without an RSV-coded hospitalization. We performed gene-based testing, tissue enrichment, gene-set enrichment, and a meta-analysis of the 2 cohorts. Finally, an analysis of potential associations between the severity of RSV infection and genetic markers was performed. Results: We did not detect any significant genome-wide associations between SNPs and RSV infection or the severity of RSV. We did find potential loci associated with RSV infections on chromosome 5 in 1 cohort but failed to replicate any signals in both cohorts. Conclusions: Despite being the largest GWAS of severe RSV infection, we did not detect any genome-wide significant loci. This may be an indication of a lack of power or an absence of signal. Future studies might include mild illness and need to be larger to detect any significant associations.

Understanding the long-term epidemiology trends of RSV, influenza, and COVID-19 is essential for planning of vaccination strategies and healthcare system epidemic preparedness. This is the first study to provide a comprehensive estimation of both excess mortality and hospitalisations among adults for these respiratory viruses in a European setting. We aim to estimate excess mortality and excess hospitalisations for RSV, influenza, and COVID-19 among adults ≥18 years in Denmark from January 2015 to March 2024. This nationwide time-trend modelling study investigates weekly mortality and hospitalisation rates surpassing the seasonal baseline for RSV, influenza, and COVID-19 among adults in Denmark. Data from the Cause of Death Register, the Danish National Patient Registry, and respiratory virus surveillance data were analysed with Generalized Additive Models (GAM) using a negative binomial likelihood function, including RSV, influenza, COVID-19 variants, and time effects to account for seasonality and trend. We estimated 3944 RSV-attributed, 5675 influenza-attributed, and 5636 COVID-19-attributed deaths. Among adults aged 65 or older, the annual mortality rates were 31.2 per 100,000 for RSV, 42.9 for influenza, and 88.5 for COVID-19. Furthermore, we estimated annual admission rates for those aged 65 and older of 177.4 per 100,000 for RSV, 164.6 for influenza, and 398.7 for COVID-19. This modelling study reveals a substantial impact of RSV on individuals aged 65 and older, with a notable increase in RSV-attributed deaths and hospitalisations in recent years likely due to expanded respiratory testing after the COVID-19 pandemic. Our findings highlight the need for increased awareness in previously considered lower-risk patients, and establish benchmarks for evaluating preventive interventions. This study received funding from Independent Research Fund Denmark.

Background: Adults hospitalized with respiratory syncytial virus (RSV) face mortality risks comparable to or higher than those with influenza A or B. However, studies on the impact of bacterial co-infections on mortality are inconsistent. Methods: This multicenter cohort study included adults hospitalized with RSV, influenza A, or B over 3 years at two tertiary care hospitals. Microbiological testing, bacterial co-infections, antibiotic use, and their association with clinical outcomes were analyzed using adjusted linear and logistic regression models. Results: Of 986 patients, 352 (36%) had RSV, 347 (35%) influenza A, and 287 (29%) influenza B. The median age was 74 years, 54% were women, and 76% had at least one comorbidity. Overall, 32% had pneumonia. The prevalence of bacterial co-infections was comparable across patients with RSV (23%), influenza A (25%), and B (28%). Among patients without bacterial co-infection, antibiotic use within 48 hours remained common across all virus groups (77%, 71%, and 75%, respectively). In adjusted analyses, bacterial co-infection in patients with RSV was not associated with mortality at 14, 30, or 90 days, high-flow oxygen therapy, mechanical ventilation, or length of stay (LOS). Early antibiotic treatment was associated with prolonged LOS but not improved survival. Conclusions: Bacterial co-infections were identified in approximately one-quarter of patients with RSV, influenza A, and B. Among patients with RSV, bacterial co-infection was not associated with adverse clinical outcomes, and early antibiotic treatment did not appear to improve clinical outcomes.