Immediate post-discharge care among US adults hospitalized with respiratory syncytial virus infection.

BACKGROUND: Respiratory Syncytial Virus (RSV) is an important pathogen causing acute respiratory illnesses in adults. RSV infection can lead to severe outcomes, including hospitalizations and even death. Despite the increased recognition of the burden in older adults, immediate post-discharge care needs among adults hospitalized with RSV are not well characterized and have not been compared to other serious medical conditions (such as influenza, acute myocardial infarction (MI), and stroke) for which there have been long-standing disease prevention efforts. OBJECTIVES: This study aims to describe the immediate post-discharge care needs among adults hospitalized with RSV in the United States and descriptively compare it to those hospitalized with influenza, acute MI, or stroke. DESIGN: Retrospective observational cohort study. PATIENTS: Adults aged ≥ 18 years, hospitalized with a primary diagnosis of RSV, influenza, acute MI, or stroke from January 01, 2016, to December 31, 2019, were identified from the Premier Healthcare Database using the International Classification of Diseases (ICD-10) codes. MAIN MEASURES: Immediate post-discharge care was categorized into three different levels of care based on the discharge dispositions. Descriptive analyses were performed. KEY RESULTS: In total, 3,629 RSV, 303,577 influenza, 388,682 acute MI, and 416,750 stroke hospitalizations were identified, the majority occurred among patients aged ≥ 65 years. Professional home care needs were the highest for RSV hospitalizations (19.1%), followed by influenza (17.7%), stroke (15.4%), and acute MI (9.8%). Additionally, institutional care needs immediately following discharge were similar for RSV, influenza, and acute MI hospitalizations (14.2%, 15.8%, and 14.1%, respectively). CONCLUSIONS: Immediate post-discharge care needs among adults hospitalized with RSV, especially in older adults, can be considerable and comparable to influenza and acute MI discharges. With recently approved RSV vaccines, efforts to increase vaccination in older adults are needed to prevent RSV and associated healthcare consequences.

Estimating the burden of vaccine preventable lower respiratory tract disease in primary care, UK: protocol for a prospective surveillance study (AvonCAP GP2).

BACKGROUND: The true burden of acute lower respiratory tract diseases (aLRTD; includes acute lower respiratory tract infection, acute exacerbation of pre-existing heart failure and chronic lung disease) among adults presenting to primary care, and the proportion that are potentially vaccine preventable, is unknown. AIMS: To describe aLRTD incidence in adults presenting to primary care; estimate proportions caused by RSV, SARS-CoV-2 and pneumococcus; and investigate disease burden from patient and NHS perspectives. DESIGN & SETTING: Primary care prospective cohort study conducted in six representative General Practices (total Ì´83 000 registered adults) in Bristol, UK. METHOD: Adults (aged≥18 years) registered at participating General Practices and presenting to primary care (in-hours or out-of-hours) or emergency department (if not admitted) with aLRTD will be eligible and identified by real-time primary care record searches. Researchers will screen electronic GP records, including free text, contact patients to assess eligibility, and offer enrolment in a surveillance study and an enhanced diagnostic study (urine, saliva and respiratory samples; physical examination; and symptom diaries). Data will be collected for all aLRTD episodes, with patients assigned to one of three arms: surveillance, embedded diagnostic, and descriptive dataset. Outcome measures will include clinical and pathogen defined aLRTD incidence rates, symptom severity and duration, NHS contacts and costs, health-related quality of life changes, and mortality (≤30 days post identification). CONCLUSION: This comprehensive surveillance study of adults presenting to primary care with aLRTD, with embedded detailed data and sample collection, will provide an accurate assessment of aLRTD burden due to vaccine preventable infections.

Burden of Respiratory Syncytial Virus (RSV) Infection Among Adults in Nursing and Care Homes: A Systematic Review.

BACKGROUND: Older adults in nursing and care homes (NCHs) are vulnerable to severe respiratory syncytial virus (RSV) infection, hospitalization, and death. This study aimed to gather data on RSV disease among older adults in NCHs and identify reported risk factors for RSV hospitalization and case fatality. METHODS: The study protocol was registered in PROSPERO (CRD42022371908). We searched MEDLINE, EMBASE, and Global Health databases to identify articles published between 2000 and 2023. Observational and experimental studies conducted among older adults in NCHs requiring assistive care and reporting RSV illness were included and relevant data were extracted. RESULTS: Of 18,690 studies screened, 32 were selected for full-text review, and 20 were included. Overall, the number of NCH residents ranged from 42 to 1459 with a mean age between 67.6 and 85 years. Attack rates ranged from 6.7% to 47.6% and annual incidence ranged from 0.5% to 14%. Case fatality rates ranged from 7.7% to 23.1%. We found similar annual incidence rates of RSV-positive acute respiratory infection (ARI) of 4582 (95% CI: 3259-6264) and 4785 (95% CI: 2258-10,141) per 100,000 reported in two studies. Annual incidence rate of RSV-positive lower respiratory tract infection was 3040 (95% CI: 1986-4454) cases per 100,000 adults. Annual RSV-ARI hospital admission rates were between 600 (95% CI: 190-10,000) and 1104 (95% CI: 350-1930) per 100,000 person-years. Among all RSV disease cases, commonly reported chronic medical conditions included chronic obstructive pulmonary disease (COPD), heart failure, ischemic heart disease, coronary artery disease, hypertension, diabetes, kidney dysfunction, cerebrovascular accident, malignancies, dementia, and those with a Charlson comorbidity score > 6.5. CONCLUSION: Data on RSV infection among NCH residents are limited and largely heterogeneous but document a high risk of illness, frequent hospitalization, and high mortality. Preventive interventions, such as vaccination, should be considered for this high-risk population. Nationally representative epidemiologic studies and NCH-based viral pathogen surveillance could more precisely assess the burden on NCH residents.

Annual public health and economic burden of medically attended respiratory syncytial virus illnesses among US adults.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease (LRTD) among adults and can lead to serious morbidity and mortality; however, evidence on the magnitude of the public health and economic burden of adult RSV-LRTD is limited. This study was undertaken to project annual clinical outcomes and economic costs of medically attended RSV-LRTD among US adults, and to identify subgroups responsible for a disproportionate share of disease burden. METHODS: Clinical outcomes of RSV-LRTD were projected for subgroups of US adults defined by age and comorbidity profile (with vs. without chronic/immunocompromising medical conditions) based on corresponding population sizes, episode (disease) rates, and case-fatality rates. Economic costs comprised medical (i.e., direct) costs and non-medical (i.e., indirect) costs of RSV-LRTD, and were generated based on numbers of episodes and unit costs in relation to setting of care, age, and comorbidity profile. RESULTS: Among 265 million US adults aged ≥18 years in 2023, 6.5 million medically attended episodes of RSV-LRTD were projected to occur including 349,260 requiring hospitalization, 357,892 requiring an emergency department visit (not leading to hospitalization), and 5.8 million requiring other ambulatory care. Direct costs ($15.2 billion) and indirect costs ($9.7 billion) were projected to total $25.0 billion. Persons aged 60-99 years accounted for 31 % of the adult population and over 50 % of the economic burden of RSV-LRTD, while adults aged <60 years with chronic/immunocompromising medical conditions accounted for 10 % of the population and 27 % of the economic burden. CONCLUSIONS: Annual burden of RSV-LRTD among US adults-especially older adults and those of all ages with underlying medical conditions-is substantial. Preventive measures, such as recently approved RSV vaccines, have the potential to yield important improvements in public and patient health, and to reduce the economic burden of RSV-LRTD from the US healthcare system and societal perspectives.

A Model-Based Estimation of RSV-Attributable Incidence of Hospitalizations and Deaths in Italy Between 2015 and 2019.

INTRODUCTION: Respiratory syncytial virus (RSV) incidence is known to be underestimated in adults due to its infrequent diagnostic testing and lower sensitivity of single nasal/nasopharyngeal swab PCR testing outside of the early childhood period. RSV can trigger acute cardiac events as well as cause respiratory disease. Consequently, we used a model-based study to estimate RSV-attributable hospitalization and mortality incidence among adults in Italy between 2015 and 2019. METHODS: Through a database predisposed by CREA Sanità, by extracting monthly data from the Italian hospitalization collection data of the Ministry of Health and the Italian National Institute of Statistics (ISTAT) data (mortality), we estimated yearly RSV-attributable incidence of events for different cardiorespiratory outcomes. We used a quasi-Poisson regression model, which accounted for periodic and aperiodic time trends and viral activity proxies. RESULTS: The yearly RSV-attributable cardiorespiratory hospitalization incidence increased with age and was highest among adults aged ≥ 75 years (1064-1527 cases per 100,000 person-years). Similarly, the RSV-attributable cardiorespiratory mortality rate was highest among persons aged ≥ 75 years (59-85 deaths per 100,000 person-years). Incidence rates for RSV-attributable hospitalizations and RSV-attributable mortality were on average 2-3 times higher for cardiorespiratory than respiratory disease alone. Incidence rate based on RSV-specific ICD codes only were 405-1729 times lower than modeled estimates accounting for untested events. CONCLUSION: RSV causes a substantial disease burden among adults in Italy and contributes to both respiratory and cardiovascular conditions. Our results emphasize the need for effective RSV prevention strategies, particularly among older adults.

Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.

INTRODUCTION: Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated. METHODS: A literature review from PubMed and Google Scholar (1985-2023) was performed and extended using snowballing from references in captured publications. RESULTS: RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines. CONCLUSIONS: RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.

RSV Risk Profile in Hospitalized Adults and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

INTRODUCTION: We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. METHODS: This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission < 30 days) and compared severity between RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. RESULTS: We included 706 RSV patients (635 inpatients and 71 outpatients), and 598 influenza and 60 COVID-19 hospitalized controls with comparable sociodemographic profile. Among RSV patients, 96 (15%) had a subtype identified: 56% A, 42% B, and 2% A + B. Eighty-one percent of RSV patients had cardiovascular conditions, 65% endocrine/metabolic, 46% chronic lung, and 43% immunocompromising conditions. Thirty-six percent were coinfected (vs. 21% influenza and 20% COVID-19; p = < .0001 and 0.01). Ninety-two percent had signs of lower respiratory infection (vs. 85% influenza and 72% COVID-19, p = < .0001) and 27% cardiovascular signs (vs. 20% influenza and 8% COVID-19, p = 0.0031 and 0.0009). Laboratory parameters of anemia, inflammation, and hypoxemia were highest in RSV. Among RSV, being a previous smoker (adjusted OR 2.81 [95% CI 1.01, 7.82]), coinfection (4.34 [2.02, 9.34]), and having cardiovascular (3.79 [2.17, 6.62]), neurologic (2.20 [1.09, 4.46]), or chronic lung (1.93 [1.11, 3.38]) diseases were risks for hospitalization. Being resident in care institutions (1.68 [1.09, 2.61]) or having a coinfection (1.91[1.36, 2.69]) were risks for higher severity, while RSV subtype was not associated with severity. Whereas RSV and influenza patients did not show differences in severity, RSV patients had 68% (38-84%) lower odds of experiencing any severe outcome compared to COVID-19. CONCLUSIONS: RSV especially affects those with comorbidities, coinfections, and living in care institutions. RSV vaccination could have an important public health impact in this population.

Relative Contribution of Diagnostic Testing to the Diagnosis of Respiratory Syncytial Virus in Hospitalized Adults in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden. METHODS: We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens. RESULTS: Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59). CONCLUSIONS: The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.

Estimated Incidence of Hospitalizations Attributable to RSV Infection Among Adults in Ontario, Canada, Between 2013 and 2019.

INTRODUCTION: Adult respiratory syncytial virus (RSV) burden is underestimated due to non-specific symptoms, limited standard-of-care and delayed testing, reduced diagnostic test sensitivity-particularly when using single diagnostic specimen-when compared to children, and variable test sensitivity based on the upper airway specimen source. We estimated RSV-attributable hospitalization incidence among adults aged ≥ 18 years in Ontario, Canada, using a retrospective time-series model-based approach. METHODS: The Institute for Clinical Evaluative Sciences data repository provided weekly numbers of hospitalizations (from 2013 to 2019) for respiratory, cardiovascular, and cardiorespiratory disorders. The number of hospitalizations attributable to RSV was estimated using a quasi-Poisson regression model that considered probable overdispersion and was based on periodic and aperiodic time trends and viral activity. As proxies for viral activity, weekly counts of RSV and influenza hospitalizations in children under 2 years and adults aged 60 years and over, respectively, were employed. Models were stratified by age and risk group. RESULTS: In patients ≥ 60 years, RSV-attributable incidence rates were high for cardiorespiratory hospitalizations (range [mean] in 2013-2019: 186-246 [215] per 100,000 person-years, 3‒4% of all cardiorespiratory hospitalizations), and subgroups including respiratory hospitalizations (144-192 [167] per 100,000 person-years, 5‒7% of all respiratory hospitalizations) and cardiovascular hospitalizations (95-126 [110] per 100,000 person-years, 2‒3% of all cardiovascular hospitalizations). RSV-attributable cardiorespiratory hospitalization incidence increased with age, from 14-18 [17] hospitalizations per 100,000 person-years (18-49 years) to 317-411 [362] per 100,000 person-years (≥ 75 years). CONCLUSIONS: Estimated RSV-attributable respiratory hospitalization incidence among people ≥ 60 years in Ontario, Canada, is comparable to other incidence estimates from high-income countries, including model-based and pooled prospective estimates. Recently introduced RSV vaccines could have a substantial public health impact.

Respiratory Syncytial Virus Sequelae Among Adults in High-Income Countries: A Systematic Literature Review and Meta-analysis.

INTRODUCTION: Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1 year following RSV-related hospitalization or resolution of acute infection. METHODS: Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible. RESULTS: Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95% CI 27.6-39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6 months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95% CI 1.0-2.0) and for readmission (general population) 1.2 (95% CI 1.1-1.3). CONCLUSIONS: Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates.

Best Practices for Identifying Hospitalized Lower Respiratory Tract Infections Using Administrative Data: A Systematic Literature Review of Validation Studies.

INTRODUCTION: Estimating the burden of lower respiratory tract infections (LRTIs) increasingly relies on administrative databases using International Classification of Diseases (ICD) codes, but no standard methodology exists. We defined best practices for ICD-based algorithms that estimate LRTI incidence in adults. METHODS: We conducted a systematic review of validation studies assessing the use of ICD code-based algorithms to identify hospitalized LRTIs in adults, published in Medline, EMBASE, and LILACS between January 1996 and January 2022, according to PRISMA guidelines. We assessed sensitivity, specificity, and other accuracy measures of different algorithms. RESULTS: We included 26 publications that used a variety of ICD code-based algorithms and gold standard criteria, and 18 reported sensitivity and/or specificity. Sensitivity was below 80% in 72% (38/53) of algorithms and specificity exceeded 90% in 77% (37/48). Algorithms for all-cause LRTI (n = 18) that included only pneumonia codes in primary position (n = 3) had specificity greater than 90% but low sensitivity (55-72%). Sensitivity increased by 5-15%, with minimal loss in specificity, with the addition of primary codes for severe pneumonia (e.g. sepsis) while pneumonia codes were in secondary position, and by 13% with codes from LRTI-related infections (e.g. viral) or other respiratory diseases (e.g. empyema). Sensitivity increased by 8% when pneumonia codes were in any position, but specificity was not reported. In hospital-acquired pneumonia and pneumococcal-specific pneumonia, algorithms containing only nosocomial- or pathogen-specific ICD codes had poor sensitivity, which improved when broader pneumonia codes were added, in particular codes for unspecified organisms. CONCLUSION: Our systematic review highlights that most ICD code-based algorithms are relatively specific, but miss a substantial number of hospitalized LRTI adult cases. Best practices to estimate LRTI incidence in this population include the use of all pneumonia ICD codes for any LRTI outcome and, to a lesser extent, those for other LRTI-related infections or respiratory diseases.

Estimation of Symptomatic Respiratory Syncytial Virus Infection Incidence in Adults in Multiple Countries: A Time-Series Model-Based Analysis Protocol.

INTRODUCTION: Estimating respiratory syncytial virus (RSV) burden in adults is challenging because of non-specific symptoms, infrequent standard-of-care testing, resolution of viral shedding before seeking medical care, test positivity that varies by specimen site in the upper airway and lower diagnostic test sensitivity compared to children. Conducting prospective observational studies to assess RSV burden in adults is time- and resource-intensive. Thus, model-based approaches can be applied using existing data to obtain more accurate estimates of RSV burden. This protocol establishes essential elements for estimating RSV incidence rate in adults using a time series model-based approach. It can be tailored to specific databases and applied globally across countries, enabling estimation of local RSV disease burden to inform public health decision-making, including immunization policy. METHODS: Data are analysed using a quasi-Poisson regression model, considering the effect of baseline trends and pathogen co-circulation, stratified by age and risk status. Pathogen co-circulation is represented by viral proxies defined based on ICD code groupings indicating RSV and influenza-specific hospitalizations, lagged 0 up to 4 weeks based on the model selection. A final model is constructed in two steps: optimization of the time trend (using p-values) and selection of the viral proxy lag time (using test statistics, to prioritize the most biologically plausible option). The yearly incidence rate and percentage of events attributable to RSV are estimated from the final model. Confidence intervals are calculated using residual bootstrapping. PLANNED OUTCOMES: Outcomes to be modelled are based on administrative ICD code groupings and include the number of cardiorespiratory, respiratory and cardiovascular events in a specific care setting (e.g., general practitioner visit, emergency department visit, hospitalization and death). Cardiovascular events are limited to those for which existing evidence suggests an association with RSV infection. Additional secondary outcomes are constructed as a subset of the primary outcomes based on specific ICD code groups.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019.

INTRODUCTION: Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany. METHODS: Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2 years and adults ≥ 60 years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities). RESULTS: Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60 years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44 year old persons (five to sixfold higher) than in ≥ 75 year old persons (two to threefold higher). CONCLUSIONS: This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60 years and among adults with underlying risk factors.

Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase.

Background: Estimates of the cost of medically attended lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) in adults, especially beyond the acute phase, is limited. This study was undertaken to estimate the attributable costs of RSV-LRTI among US adults during, and up to 1 year after, the acute phase of illness. Methods: A retrospective observational matched-cohort design and a US healthcare claims repository (2016-2019) were employed. The study population comprised adults aged ≥18 years with RSV-LRTI requiring hospitalization (RSV-H), an emergency department visit (RSV-ED), or physician office/hospital outpatient visit (RSV-PO/HO), as well as matched comparison patients. All-cause healthcare expenditures were tallied during the acute phase of illness (RSV-H: from admission through 30 days postdischarge; ambulatory RSV: during the episode) and long-term phase (end of acute phase to end of following 1-year period). Results: The study population included 4526 matched pairs of RSV-LRTI and comparison patients (RSV-H: n = 970; RSV-ED: n = 590; RSV-PO/HO: n = 2966). Mean acute-phase expenditures were $42 179 for RSV-H (vs $5154 for comparison patients), $4409 for RSV-ED (vs $377), and $922 for RSV-PO/HO (vs $201). By the end of the 1-year follow-up period, mean expenditures-including acute and long-term phases-were $101 532 for RSV-H (vs $36 302), $48 701 for RSV-ED (vs $27 131), and $28 851 for RSV-PO/HO (vs $20 523); overall RSV-LRTI attributable expenditures thus totaled $65 230, $21 570, and $8327, respectively. Conclusions: The cost of RSV-LRTI requiring hospitalization or ambulatory care among US adults is substantial, and the economic impact of RSV-LTRI may extend well beyond the acute phase of illness.

Estimated Respiratory Syncytial Virus-Related Hospitalizations and Deaths Among Children and Adults in Spain, 2016-2019.

INTRODUCTION: Respiratory syncytial virus (RSV) causes a substantial disease burden among infants. In older children and adults, incidence is underestimated due to nonspecific symptoms and limited standard-of-care testing. We aimed to estimate RSV-attributable hospitalizations and deaths in Spain during 2016-2019. METHODS: Nationally representative hospitalization and mortality databases were obtained from the Ministry of Health and the National Statistical Office. A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends and viral activity, while allowing for potential overdispersion. RESULTS: In children, the RSV-attributable respiratory hospitalization incidence was highest among infants aged 0-5 months (3998-5453 cases/100,000 person-years, representing 72% of all respiratory hospitalizations) and decreased with age. In 2019, estimated rates in children 0-5, 6-11, 12-23 months and 6-17 years were approximately 1.3, 1.4, 1.5, and 6.5 times higher than those based on standard-of-care RSV-specific codes. In adults, the RSV-attributable cardiorespiratory hospitalization rate increased with age and was highest among persons ≥ 80 years (1325-1506 cases/100,000, 6.5% of all cardiorespiratory hospitalizations). In 2019, for persons aged 18-49, 50-59, 60-79, and ≥ 80 years, estimated rates were approximately 8, 6, 8, and 16 times higher than those based on standard-of-care RSV-specific codes. The RSV-attributable cardiorespiratory mortality rate was highest among ≥ 80 age group (126-150 deaths/100,000, 3.5-4.1% of all cardiorespiratory deaths), when reported mortality rate ranged between 0 and 0.5/100,000. CONCLUSIONS: When accounting for under-ascertainment, estimated RSV-attributable hospitalizations were higher than those reported based on standard-of-care RSV-specific codes in all age groups but particularly among older children and older adults. Like other respiratory viruses, RSV contributes to both respiratory and cardiovascular complications. Efficacious RSV vaccines could have a high public health impact in these age and risk groups.

Surveillance of pneumococcal serotypes in adults hospitalised with acute lower respiratory tract infection in Bristol, UK.

INTRODUCTION: Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. METHODS: A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). RESULTS: Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DISCUSSION: Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

Rates of Lower Respiratory Tract Illness in US Adults by Age and Comorbidity Profile.

INTRODUCTION: While it is widely recognized that older adults, adults with chronic medical conditions (CMC), and adults with immunocompromising conditions (IC) are at increased risk of lower respiratory tract illness (LRTI), evidence of the magnitude of increased risk is limited. This study was thus undertaken to characterize rates of hospitalized and ambulatory LRTI among United States (US) adults by age and comorbidity profile. METHODS: A retrospective cohort design and US healthcare claims database (2016-2019) were employed. Study population included adults aged ≥ 18 years and was stratified by age and comorbidity profile (CMC-, CMC+ , IC). LRTI was ascertained overall and by pathogen pathogen (e.g., respiratory syncytial virus [RSV]), and was classified by care setting (hospital, emergency department [ED], physician office/hospital outpatient [PO/HO]). RESULTS: Relative rates (RR) of LRTI generally increased with older age across care settings (vs. 18-49 years), with the most marked increase for hospitalizations: for LRTI-hospitalized, RRs ranged from 3.3 for 50-64 years to 46.6 for ≥ 85 years; for LRTI-ED and LRTI-PO/HO, RRs ranged from 1.0 to 2.7 and from 1.3 to 1.5, respectively. Within age groups, LRTI rates were also consistently higher among CMC+ and IC adults (vs. CMC- adults). Age-specific RRs of LRTI patients hospitalized due to RSV were largely comparable to overall LRTI; age-specific RRs for other care settings, and RRs for CMC+ and IC adults (vs. CMC- adults), were generally higher for LRTI due to RSV. CONCLUSIONS: Incidence of LRTI, including that due to RSV, especially for events requiring acute inpatient care, is markedly higher among older adults and adults of all ages with CMC or IC.

Influenza Vaccine Effectiveness Pre-pandemic Among Adults Hospitalized With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease and Older Adults.

BACKGROUND: Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. METHODS: We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). RESULTS: Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8-75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9-72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3-93.9%). CONCLUSIONS: Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018-2020 seasons.

Effectiveness of Immunization Products Against Medically Attended Respiratory Syncytial Virus Infection: Generic Protocol for a Test-Negative Case-Control Study.

Monitoring the real-life effectiveness of respiratory syncytial virus (RSV) products is of major public health importance. This generic protocol for a test-negative design study aims to address currently envisioned approaches for RSV prevention (monoclonal antibodies and vaccines) to study effectiveness of these products among target groups: children, older adults, and pregnant women. The generic protocol approach was chosen to allow for flexibility in adapting the protocol to a specific setting. This protocol includes severe acute respiratory infection (SARI) and acute respiratory infection (ARI), both due to RSV, as end points. These end points can be applied to studies in hospitals, primarily targeting patients with more severe disease, but also to studies in general practitioner clinics targeting ARI.

Effectiveness of Vaccines and Monoclonal Antibodies Against Respiratory Syncytial Virus: Generic Protocol for Register-Based Cohort Study.

Several immunization products are currently being developed against respiratory syncytial virus (RSV) for children, pregnant females, and older adults, and some products have already received authorization. Therefore, studies to monitor the effectiveness of these products are needed in the following years. To assist researchers to conduct postmarketing studies, we developed a generic protocol for register-based cohort studies to evaluate immunization product effectiveness against RSV-specific and nonspecific outcomes. To conduct a study on the basis of this generic protocol, the researchers can use any relevant databases or healthcare registers that are available at the study site.