Underreporting and Misclassification of Respiratory Syncytial Virus-Coded Hospitalization Among Adults in Denmark Between 2015-2016 and 2017-2018.

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-Associated Hospitalization in Adults With Comorbidities in 2 European Countries: A Modeling Study.

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.

Genome-Wide Association study of susceptibility to respiratory syncytial virus hospitalization in young children < 5 years of age.

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 two Danish cohorts. We compared SNPs from 1786 children hospitalized with RSV to 45,060 controls without a RSV-coded hospitalization. We performed gene-based testing, tissue-enrichment, gene-set enrichment, and a meta-analysis of the two 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 one cohort, however, we failed to replicate any signals in both cohorts. CONCLUSION: 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.

A Retrospective Cohort Study on Infant Respiratory Tract Infection Hospitalizations and Recurrent Wheeze and Asthma Risk: Impact of Respiratory Syncytial Virus.

BACKGROUND: Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections. METHODS: We performed a retrospective cohort study using Danish national hospital discharge registers. Infants younger than 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, nonpathogen-coded lower respiratory tract infections (LRTI), pertussis, or nonspecific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5-minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF). RESULTS: We included 68 130 infants, of whom 20 920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR, 2.69; 95% confidence interval [CI], 2.48-2.92), AURTI (CIRR, 1.48; 95% CI, 1.34-1.58), or pertussis (CIRR, 2.32; 95% CI, 1.85-2.91), similar to pneumonia and other respiratory pathogens (CIRR, 1.15; 95% CI, .99-1.34) and LRTI (CIRR, 0.79; 95% CI, .60-1.04), but lower than nonspecific respiratory infections (CIRR, 0.79; 95% CI, .73-.87). Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI, 2.08-2.70) for 0 to <1 year to 1.23 (95% CI, .88-1.73) for 6 to <10 years for term-born children, and from 1.48 (95% CI, 1.09-2.00) to 0.60 (95% CI, .25-1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors. CONCLUSIONS: Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly at preschool age. If causal, RSV prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma.

Estimating future smoking in Danish youth - effects of three prevention strategies.

Aims: Preventing smoking and aiding cessation among youth and young adults carries the possibility of reducing future smoking prevalence significantly. This paper estimates the impact on future smoking prevalence of 25 year olds by increasing tobacco prices, securing indoor smoke-free homes and implementing school-based multi-tiered interventions. Methods: Utilizing a multi-state Markov model, a status quo projection of the smoking prevalence from years 2017 to 2030 were compared with projections of the smoking prevalence in 2030 considering the impact of the three prevention strategies. Results: In a status quo projection, 27.0% of Danish 25-year-old females are expected to be smokers in 2030, while 13.2% would be smokers in 2030 were all three prevention strategies in effect from 2019. By itself, increasing tobacco prices by 50% reduced the prevalence of smokers among 25-year-old females to 14.8% in 2030, a relative reduction of 47.5%. For 25-year-old males in 2030 the reductions were similar, with a prevalence of 16.6% when all three prevention strategies were in effect, a relative reduction of 51.5%. Conclusions: Implementing increasing tobacco prices, indoor smoke-free homes and school-based multi-tiered interventions in Denmark is likely to significantly decrease youth smoking prevalence in the future. However, these three strategies will not produce a smoke-free generation without other initiatives.

Where Birth Month, Sex and Age Matters: The Burden of Severe Respiratory Disease in Danish Children <5 Years, 2016-2022.

BACKGROUND: In light of the substantial impact that respiratory diseases in young children poses on healthcare systems globally, and in the wake of the recent COVID-19 pandemic, there is a growing urgency to obtain reliable estimates on the burden of respiratory disease. OBJECTIVES: The aim of this study is to quantify the overall burden of respiratory disease requiring hospitalizations and explore the trends in these admissions in Danish children <5 years, January 1, 2016-October 31, 2022. METHODS: The number of hospitalizations attributed to respiratory infections in children <5 years, was extracted from the Danish National Patient Register, and stratified into subgroups based on age, gender and birth month, and presented on a month-to-month basis. RESULTS: A total of 48,194 children under the age of 5, were hospitalized due to respiratory infections within the study period and the annual hospitalization incidence exhibited a noteworthy variation. Risk factors associated with the highest hospitalization incidence were young age, male gender and in children under 1-year-old, birth months falling in the period of November to January. Younger age and admission during the winter months were linked to longer hospital stays. The seasonal pattern of hospitalizations and the distribution of hospitalizations across various subgroups were greatly influenced by the COVID-19 pandemic. CONCLUSION: This study describes and quantifies the importance of factoring in specific child demographics and seasonal variations in hospitalizations when devising preventive healthcare strategies such as the use of monoclonal antibody therapy and vaccines.

Hospitalisation at Home of Patients with COVID-19: A Qualitative Study of User Experiences.

Hospitalisation at Home (HaH) is a new model providing hospital-level care at home as a substitute for traditional care. Biometric monitoring and digital communication are crucial, but little is known about user perspectives. We aim to explore how in-patients with severe COVID-19 infection and clinicians engage with and experience communication and self-monitoring activities following the HaH model. A qualitative study based on semi-structured interviews of patients and clinicians participating in the early development phase of HaH were conducted. We interviewed eight clinicians and six patients. Five themes emerged from clinicians: (1) staff fear and concerns, (2) workflow, (3) virtual closeness, (4) patient relatives, and (5) future HaH models; four themes emerged from patients: (1) transition to home, (2) joint responsibility, (3) acceptability of technologies, and (4) relatives. Despite technical problems, both patients and clinicians were enthusiastic about the conceptual HaH idea. If appropriately introduced, treatment based on self-monitoring and remote communication was perceived acceptable for the patients; however, obtaining vitals at night was an overwhelming challenge. HaH is generally acceptable, perceived patient-centred, influencing routine clinical workflow, role and job satisfaction. Therefore, it calls for educational programs including more perspective than issues related to technical devices.

Prevalence and duration of anti-SARS-CoV-2 antibodies in healthcare workers.

INTRODUCTION: Knowledge of the seroprevalence and duration of antibodies against SARS-CoV-2 was needed in the early phases of the COVID-19 pandemic and is still necessary for policy makers and healthcare professionals. This information allows us to better understand the risk of reinfection in previously infected individuals. METHODS: We investigated the prevalence and duration of detectable antibodies against SARS-CoV-2 in sequentially collected samples from 379 healthcare professionals. RESULTS: SARS-CoV-2 seroprevalence at inclusion was 5.3% (95% confidence interval (CI): 3.3-8.0%) and 25% of seropositive participants reverted during follow-up. At the end of follow-up, the calculated probability of having detectable antibodies among former seropositive participants was 72.2% (95% CI: 54.2-96.2%). CONCLUSION: Antibodies against SARS-CoV-2 were detectable in a subset of infected individuals for a minimum of 39 weeks. FUNDING: The assays performed at Rigshospitalet were developed with financial support from the Carlsberg Foundation (CF20-0045) and the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201). TRIAL REGISTRATION: The study was registered with the Danish National Committee on Health Research Ethics (H-20022312).

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

Patterns of multimorbidity and demographic profile of latent classes in a Danish population-A register-based study.

BACKGROUND: Multimorbidity is an increasing public health concern and is associated with a range of further adverse outcomes. Identification of disease patterns as well as characteristics of populations affected by multimorbidity is important for prevention strategies to identify those at risk. AIM: The aim of the study was to identify and describe demographic characteristics of multimorbidity classes in three age groups (16-44 years, 45-64 years, and 65+ years). METHODS: Based on register information on 47 chronic diseases and conditions, we used latent class analysis to identify multimorbidity classes in a random sample of the Danish population (n = 470,794). Information on sociodemographic characteristics (age, sex, region of origin, educational level, employment status, and marital status) was obtained from registers and linked to the study population. Age- and sex-adjusted multinomial logistic regression models were used to examine associations between multimorbidity classes and sociodemographic characteristics. RESULTS: We identified seven classes among individuals in the age groups 45-64 years and 65+ years and five classes in the age group 16-44 years. Overall, the classes were similar in the three age groups, but varied in size, i.e. the class 'No or few diseases' was larger in the younger age group. The class 'Many diseases' (a class with both somatic diseases and mental illnesses) was only seen in individuals aged 45-64 years and 65+ years. There were social inequalities in odds of belonging to the multimorbidity classes compared to the healthier class. These social inequalities varied but were especially strong in the classes named 'Many diseases' and 'Mental illness, epilepsy'. CONCLUSION: The results of the study suggest that there are social inequalities in multimorbidity but that these inequalities are not universal to all types of multimorbidity. This supports that multimorbidity is diverse and should be prevented and treated accordingly.