Respiratory Syncytial Research Articles

Hospitalizations for bronchiolitis among infants before and after the SARS-CoV-2 pandemic: an area-based study of the Emilia-Romagna Region, Italy

BackgroundBronchiolitis is the most frequent lower respiratory tract infection and a leading cause of hospitalization in infants. Our aim was to assess the incidence and characteristics of bronchiolitis requiring hospital admission in an Italian region before and after the SARS-CoV-2 pandemic.MethodsThis area-based retrospective study analyses 4,396 hospital discharge records (HDR) of children under 1 year of age admitted with a diagnosis of bronchiolitis (ICD9-CM codes 466.11 and 466.19), in Emilia-Romagna (Italy) from January1st, 2018 to December 31th, 2021. Weighted t-testing and Z-testing was carried out.Resultsin the study period, 2–4% of infants were admitted for bronchiolitis (10% of all admissions under 1 year) and 59% of them were aged less than 90 days. After a significant decrease in 2020, bronchiolitis resurged in 2021, and Respiratory Syncytial Virus (RSV) cases reached 82%. RSV cases were more likely to undergo non-invasive ventilation (NIV), oxygen supplementation and to receive i.v. (intravenous) infusions. There was an overall increasing trend in NIV and oxygen supplementation, and a decreasing trend in chest X-rays.ConclusionsThis area-based study shows reduced hospital admissions due to bronchiolitis during the SARS-CoV-2 pandemic and a resurgence of RSV infection after the easing of preventive measures. We also provide information on length of stay and need for hospital treatments. These area-based information will be helpful in assessing the impact of future universal prevention measures.

Respiratory pathogen spectrum and epidemiological trends in Hainan Province: a retrospective analysis from 2017 to 2023

BackgroundRespiratory tract infections (RTIs) pose a significant global health burden, caused by various pathogens. The COVID-19 pandemic and non-pharmaceutical interventions (NPIs) have created unprecedented challenges for public health systems, inadvertently altering the dynamics of other respiratory pathogens. This study aims to illustrate changes in the pathogen spectrum among RTI patients in Hainan Province before and during the pandemic.MethodsA retrospective study was conducted to demonstrated the epidemiology characteristics of respiratory pathogens across pre-COVID-19, NPI and COVID-19 pandemic in Hainan from 2017 to 2023. A total of 21,036 patients with RTI of all age groups were enrolled and tested for nine common pathogens: influenza A virus (Flu-A), influenza B virus (Flu-B), parainfluenza virus (PIV), Adenovirus (AAV), respiratory syncytial virus (RSV), Q fever Rickettsiae (Q Fever), Legionella pneumophila (L. pne), Chlamydia pneumoniae (C. pne), and Mycoplasma pneumoniae (M. pne).ResultsDuring 2017–2023, the number of RTI patients and pathogen detection rate was gradually decrease from 33.30% (3,886/11,670; pre-COVID-19), to 30.81% (2,034/6,602; NPI) and 22.43% (620/2,764; COVID-19). M. pne (25.52%), Flu-B (3.9%), and PIV (3.12%) were identified as the most prevalent pathogens across three periods. However, the infection rate for M. pne was significantly decrease, and the infection rate for Flu-B and Flu-A were a notable increased in NPI and COVID-19 pandemic. Children aged 0–5 years account for the largest proportion of all RTI patients with the highest infection rate, especially in NPI and COVID-19 pandemic. Flu-A, Flu-B, and RSV exhibited spring-specific seasonal prevalence during NPI and COVID-19 pandemic. Co-infection pattern analysis showed that “M. pne-dominant viruses” co-infection type was prevalent across all three time periods.ConclusionM. pne, Flu-B, Flu-A, and PIV were found to be the main causative pathogens of RTI patients in Hainan Province, and their prevalence levels and seasonal patterns had changed during large-scale NPI and COVID-19 pandemic.

Impact of enhanced public health and infection control measures on pediatric hospital-acquired respiratory viral infections during the SARS-CoV-2 pandemic.

Visitor restrictions and mask-wearing may reduce hospital-acquired infections (HAI) as part of infection control bundles. The impact of a strict visitor policy and compulsory surgical mask wearing implemented during the SARS-CoV-2 pandemic, but prior to any local community circulating SARS-CoV-2, on the rates of hospital-acquired respiratory viral infections (HA-RVI) was assessed. Retrospective audit of a local HAI database for HA-RVI from 1st April 2019 to 29th March 2021 in a tertiary children's hospital. HA-RVI were standardized against occupied bed days (OBD) and admitted community acquired infections (CAI). Rates of HA-RVI were compared during 52 weeks of SARS-CoV-2-associated enhanced control periods (visitor restrictions with and without universal surgical masking), against 52 weeks standard practice. Total respiratoryvirus infections, respiratory syncytial virus (RSV), and rhinovirus infections were analysed. Comparing standard practice with enhanced measures, 42 v 15 HA-RVI and 1517 v 691 CAI were noted. Enhanced infection controls resulted in significant reductions in total HA-RVI when adjusted for OBD (p=0.0038) and CAI (p=0.0122). Non-significant decreases were seen in hospital-acquired respiratory syncytial virus (HA-RSV) adjusted for both CAI and OBD. Visitor restrictions combined with universal surgical masks significantly decreased adjusted total HA-RVI compared with visitor restrictions alone (adjusted for OBD p=0.0123; adjusted for CAI p=0.0429). HA-RSV decreased non-significantly when mask wearing was combined with visitor restrictions compared with visitor restrictions alone. HA-rhinovirus infections did not decrease with the addition of masks to visitor restrictions. Enhanced infection control measures introduced with SARS-CoV-2 pandemic decreased some HA-RVI. Universal surgical mask wearing decreased HAI rates more than visitor restrictions alone, except for rhinovirus where the HAI rate remained unchanged.

Comparison of characteristics and immune responses between paired human nasal and bronchial epithelial organoids

BackgroundThe nasal epithelium, as part of a continuous and integrated airway epithelium, provides a more accessible sample source than the bronchial epithelium. However, the similarities and differences in gene expression patterns and immune responses between these two sites have not been extensively studied.ResultsFour lines of matched nasal and bronchial airway epithelial cells obtained from the four patients were embedded in Matrigel and cultured in thechemically defined medium to generate patient-derived nasal organoids (NO) and bronchial organoids (BO). Histologic examination of nasal organoid tissue revealed high similarity and a reduced ciliary beat frequency compared to bronchial organoid tissue. Whole exome sequencing revealed that over 99% of single nucleotides were shared between the NO and matched BO and there was a 95% overlap in their RNA transcriptomes. RNA sequencing analysis of differentially expressed genes indicated a significant reduction in the immune response in NO. RSV infection revealed more productive replication in NO, with a downregulated immune pathway identified by RNA sequencing analysis and upregulated levels of pro-inflammatory cytokines in culture supernatants in NO compared to BO.ConclusionsNO and BO serve as robust in vitro models, faithfully recapitulating the biological characteristics of upper respiratory epithelial cells. The different regions of respiratory epithelial cells exhibit distinct immune responses, underscoring their complementary roles in exploring airway immune mechanisms and disease pathophysiology.

Clinical manifestations, para-clinical features and outcome of Iranian adults with respiratory syncytial virus (RSV) infection: a report from hospitalized patients

BackgroundRespiratory syncytial virus (RSV) is an important cause of children’s pulmonary infections. However, there are fewer studies on RSV infections in adults. The purpose of this study was to describe the clinical manifestations, para-clinical characteristics, and outcome of RSV infection among adult patients who were referred to the Imam Khomeini Hospital Complex during the winter and spring of 2022–2023.MethodsFrom December 21, 2022, to May 20, 2023, we conducted a cross-sectional study on hospitalized adults having positive RT-PCR results for RSV. We further assessed the clinical and para-clinical characteristics and outcomes of the RSV groups.ResultsWe screened 1375 adults with suspected acute respiratory infections (ARIs) and confirmed RSV infections in 59 of them (4.3%). Of these, 23 patients were excluded from further analysis due to outpatient management, leaving 36 hospitalized patients with confirmed RSV infection (61.01%). The mean age of the hospitalized patients was 53.28 ± 20.37 years (range: 15–83), with a slightly higher proportion of females (52.80%) compared to males (47.20%). Dyspnea, productive cough, and fever were the most common symptoms, with a mean symptom duration of 10.50 days. Ischemic heart disease, hypertension, and liver failure were common underlying conditions. Notably, biochemical and inflammatory markers such as CRP, ESR, and LDH were significantly elevated beyond the normal range. Finally, five patients (13.9%) who received intensive care treatments died.ConclusionsAlthough the rate of RSV infection was not high among Iranian adults, a greater proportion of patients required hospitalization (61%). There was a significant link between liver failure, an elevated INR, more than 30% bilateral pulmonary involvement, abdominal pain, longer ICU stays, and immunodeficiency cases with increased mortality from RSV infection. We suggest that RSV infection may act as a secondary factor in decompensating pre-existing liver failure, which was present in certain patients with underlying conditions, potentially leading to life-threatening consequences.

Knowledge and Attitudes Regarding Respiratory Syncytial Virus (RSV) Prevention: A Systematic Review

Background: New strategies for respiratory syncytial virus (RSV) prevention are available and are in development, but their acceptance is crucial to their effectiveness. Objectives: This systematic review aims to summarize current quantitative and qualitative evidence regarding knowledge and attitudes relating to RSV prevention. Methods: Six databases (PubMed, Scopus, APA PsycArticles; APA PsycInfo; CINAHL Complete; Psychology and Behavioral Sciences Collection) and two preprint repositories (medRxiv and Preprints) were searched up until 23 December 2024 (PROSPERO: CRD42024602351). Results: Sixty-one articles were included, focusing on vaccination for the elderly and adults at risk (n = 10) or pregnant people (n = 24, of which 8 also examined preferences for maternal vs. infant immunization) and infant immunization (n = 27, of which 16 focused on palivizumab, with 6 focusing on adherence to its monthly administration). Eighteen articles assessed attitudes in healthcare professionals. Overall, findings showed limited knowledge and awareness of RSV but generally positive attitudes towards prevention strategies and moderate to high intentions and uptake rates. Protection against the disease and perceived severity promoted acceptance, whereas concerns about side effects hindered it. Maternal vaccination was more acceptable than infant immunization. Conclusions: Attitudes towards RSV prevention options were generally favorable. Should more options become available, preferences may depend on which options are available, their characteristics, and how they are framed and presented. These insights highlight the importance of education on RSV grounded in decision-making literature, while recognizing the likely favorable reception of preventive measures across target age-populations.

A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus

The Food and Drug Administration (FDA) has approved vaccines designed by GSK, Pfizer and Moderna to protect high-risk populations against respiratory syncytial virus (RSV). These vaccines employ the pre-fusion F (pre-F) protein as the immunogen. In this study, we explored an mRNA vaccine based on a modified pre-F protein called LC2DM-lipid nanoparticle (LC2DM-LNP). This vaccine features a truncated version of the pre-F protein that is anchored to the cell membrane. Our experiments in young and old female mice revealed that the LC2DM-LNP vaccine elicited robust neutralizing antibody titers. Moreover, LC2DM-LNP prompted a Th1-skewed T-cell immune response in female rodent models. Female cotton rats immunized with LC2DM-LNP demonstrated strong immunity to RSV, without signs of vaccine-enhanced respiratory disease (VERD), even in cases of breakthrough infection. Importantly, when administered to pregnant female cotton rats, LC2DM-LNP ensured the transfer of pre-F-specific antibodies to the offspring and provided protection against RSV without increasing lung inflammation. Our findings suggest that LC2DM-LNP could serve as an alternative RSV vaccine candidate for high-risk groups.

Safety and Immunogenicity of Concomitant Administration and Combined Administration of Bivalent BNT162b2 COVID-19 Vaccine and Bivalent RSVpreF Respiratory Syncytial Virus Vaccine with or Without Quadrivalent Influenza Vaccine in Adults ≥ 65 Years of Age

Concomitant administration may improve vaccination rates. This analysis of a phase 1/2 randomized study included 1073 healthy ≥65-year-olds who previously received ≥3 mRNA COVID-19 vaccine doses. Participants received concomitantly administered RSVpreF and bivalent BA.4/BA.5-adapted BNT162b2 vaccine (concomitant administration) with or without quadrivalent influenza vaccine (QIV), admixed combined RSVpreF + BNT162b2 vaccine (combined vaccine) with or without QIV, RSVpreF, BNT162b2, or QIV. Immunogenicity objectives included demonstrating the noninferiority of neutralizing antibody titers elicited by concomitant administration and combined vaccine compared with RSVpreF or BNT162b2 administered alone, and by concomitant administration and combined vaccine given with QIV compared with RSVpreF, BNT162b2, and QIV alone. Reactogenicity (≤7 days) and safety ≤1 month (adverse events (AEs)) and ≤6 months (serious AEs (SAEs)) after vaccination were assessed. Noninferiority for all immunogenicity comparisons was demonstrated. All vaccine groups were well tolerated; no new safety concerns were identified. Reactogenicity was mostly mild/moderate with rates generally similar across groups, except injection site pain and fatigue, which were less frequent with RSVpreF + placebo vs. other groups. AEs were infrequent, mostly mild/moderate, occurring at similar frequencies across groups. No AEs leading to study withdrawal or vaccine-related SAEs were reported. Favorable safety and tolerability alongside similar immunogenicity provide support for concomitant or combined use of RSVpreF and BNT162b2, with or without QIV, to help protect older adults from these important respiratory pathogens (NCT05886777).

Ten-Year Surveillance of RSV Hospitalizations in Adults: Incidence Rates and Case Definition Implications.

The impact of RSV in older adults is under-recognized, and the limited existing studies on the incidence of hospitalizations show great variability. This study aims to estimate the seasonal incidence rates (IRs) of RSV hospitalizations among adults aged 60 and older (≥60) and evaluate how different case definitions influence these estimates. A prospective, multicentre observational study with active monitoring conducted over 10 seasons (2010/2011 to 2019/2020) in 4-10 hospitals (depending on the season) that covered 21-46% of the region's total population (around 5 million people). RSV-hospitalization IRs per 100,000 person-years (p-y) and 95% confidence intervals (CI) were calculated by the Exact Poisson method, and were stratified by age group (≥60, ≥70, and ≥80), RSV season, sex, and the entire study period. Two case definitions were compared: influenza-like illness (ILI) and the combined use of ILI and extended severe acute respiratory infection (ILI/SARI). A total of 40,600 hospitalizations of individuals aged ≥60 were included. The RSV-hospitalization IRs ranged from 21 to 402 per 100,000 p-y, varying by season, age group and case definition. The highest IRs were observed in those aged 80 and older. The ILI case definition underestimated RSV hospitalizations by 13% to 40% when compared to the ILI/SARI case definition. On average, approximately 1 every 1,000 adults ≥60 is hospitalized due to RSV. The risk of a severe RSV infection increases with age and varies significantly between seasons. These are key results for the estimation of the potential impact of the new available RSV vaccines.

Severity and outcomes of adult respiratory syncytial virus inpatient compared with influenza: observational study from Japan

Background Respiratory syncytial virus (RSV) significantly impacts not only children but also adults. However, knowledge of the severity and outcomes among adult RSV inpatients is still limited. Objectives To clarify the short- and long-term health threats associated with adult RSV infections. Methods This retrospective observational study included 56,980 adult inpatients aged 18 years and older due to RSV or influenza infection between April 2010 and March 2022. After inverse probability weighting adjustment, we used Poisson’s regression to estimate the risk of outcomes. Results The RSV group had a higher risk of requiring mechanical ventilation during hospitalization compared to the influenza group (9.7% vs. 7.0%; risk ratio (RR), 1.35; 95% confidence interval (CI), 1.08–1.67). In-hospital mortality was comparable between RSV and influenza groups (7.5% vs. 6.6%; RR, 1.05; 95% CI, 0.82–1.34). RSV group was associated with increased risk of readmission within 1 year after surviving discharge (34.0% vs. 28.9%; RR, 1.19; 95% CI, 1.07–1.32) and all-cause mortality within 1 year of admission (12.9% vs. 10.3%; RR, 1.17; 95% CI, 1.02–1.36). In the age-stratified analysis, the RSV group aged 60 years and older had a higher risk than the influenza group for in-hospital death, readmission and all-cause mortality within one year. Conclusions RSV infections demonstrated comparable or greater health threats than influenza infections not only during hospitalization but also in long-term outcomes. The findings underscore the threat of RSV in adults, the impact on healthcare systems and the need for continued development of public health counter measures against RSV.

Learn from international recommendations and experiences of countries that have successfully implemented monoclonal antibody prophylaxis for prevention of RSV infection.

Respiratory syncytial virus (RSV)-mediated bronchiolitis causes a significant global health burden. Despite this, for several years, the only approved agent for RSV prophylaxis was the anti-RSV monoclonal antibody Palivizumab, reserved for a small population of infants at high risk of developing severe RSV disease. Recently, the availability and approval of nirsevimab to immunize all infants against RSV infection since their first RSV season represented a crucial paradigm shift in RSV prevention. Nirsevimab has been shown to be safe and effective (> 80%) against RSV lower respiratory tract infections (LRTIs) in all infants and children at their first season of RSV. Surveillance studies have demonstrated 90% effectiveness in reducing all-cause hospitalizations, all-cause LRTI hospitalizations, RSV-related LRTI hospitalizations, and severe RSV-related LRTIs. Moreover, the consistency and reproducibility of the beneficial outcomes coming from the prophylaxis with nirsevimab highlights its potential to deliver substantial health benefits, positioning monoclonal antibody administration as a cornerstone in the fight against RSV-related morbidity and mortality. Implementing immunization strategies for infants and children is crucial to align the international experiences and guarantee universal protection. This review provided an updated overview of the monoclonal antibody strategy for preventing RSV infection.

Changes in Seasonal Patterns for Common Pediatric Respiratory Viruses During the COVID Pandemic.

Observed alterations in seasonal patterns of common pediatric respiratory viruses during and immediately after the COVID-19 pandemic had far-reaching implications for the care of ill children. Here, we quantify the effects of the pandemic and related nonpharmaceutical interventions on the prevalence and seasonality of common pediatric respiratory illnesses. We performed a retrospective chart review within a large health network to identify incidence rates of common respiratory viruses and compared them to historical trends. Time series analyses using seasonal autoregressive integrated moving average models were utilized to identify seasonal patterns for the different virus types and quantify deviations from expected incidence rates. Overall, we noted a steep decline in non-COVID viral infection rates at the onset of the COVID pandemic in March 2020, largely coincident with the institution of mask mandates and lockdown measures. This trend continued until the Spring of 2021, at which time non-COVID infections resurged to rates higher than pre-COVID levels. In addition, the historically observed seasonality of these viruses was significantly disrupted by the pandemic. In particular, the historical peaks for influenza A and human metapneumovirus shifted from February and March, respectively, to bimodal peaks in December 2021 and May 2022; respiratory syncytial virus demonstrated an unprecedented Spring/Summer season in 2021; parainfluenza type 1 was unusually active in 2022, an even-numbered year; and influenza B virtually disappeared during and immediately after the pandemic. Our observations add to the growing body of literature supporting the hypothesis that human interactions are one of the key drivers of pediatric respiratory viral seasonality in addition to climate. Understanding the effect of human interactions on disease spread is crucial for the development of effective mitigation measures for future pandemics while avoiding dangerous spikes of other illnesses once those interventions are lifted.

Viral Codetection and Clinical Outcomes of Infants Hospitalized With Bronchiolitis: A Multicenter Cohort Study.

The simultaneous identification of multiple respiratory viruses is common in infants hospitalized with respiratory tract infections. Respiratory syncytial virus (RSV) is one of the main pathogens in bronchiolitis, although codetection of rhinovirus, influenza and other respiratory viruses may occur in about one-third of cases. The relevance of viral codetection on disease severity is still controversial. This multicenter cohort study aimed to assess the clinical outcomes of infants under 24 months hospitalized with bronchiolitis, comparing those testing positive for RSV alone, RSV plus another virus and ≥2 viruses distinct from RSV. Data were collected across 13 hospitals in Lombardy, Italy, both in the prepandemic and pandemic years. Random effect regression models were also employed to test the association between 3 groups (infants testing positive for RSV alone, RSV plus another respiratory virus and no RSV but ≥2 respiratory viruses other than RSV) and course of bronchiolitis, adjusted for potential confounders. Among 1788 infants, 86.7% tested positive for RSV alone, 6.9% for RSV plus another virus and 6.3% for ≥2 other viruses. Significant differences were found in clinical outcomes: infants with multiple non-RSV viruses had shorter oxygen supplementation, intensive care and hospital stay compared with those with RSV alone. Notably, codetection of RSV and another virus was associated with a higher risk of radiologically confirmed pneumonia, whereas detection of ≥2 non-RSV viruses was inversely associated with pneumonia. These findings point out that codetection of viruses other than RSV is associated with milder disease courses than detection of RSV alone in infants with bronchiolitis. On the other hand, patients with RSV and another virus are at higher risk of pneumonia than infants affected by RSV alone. Further research is required to understand the underlying mechanisms and optimize management strategies in infants with bronchiolitis testing positive for multiple viruses.

Differential Pattern of Symptom Correlation With Acute Respiratory Infections in Korea.

Acute respiratory infections (ARIs) pose global health challenges, with major outbreaks affecting healthcare systems and resulting in significant morbidity and mortality. We aimed to identify distinctive signs or symptoms correlated with ARIs for utilizing syndromic surveillance. We used data from national Korean databases to examine correlations between various symptoms and the reported ARI viruses in children aged under and over 5 years. In children under 5 years old, respiratory symptoms were strongly correlated with human adenovirus, human respiratory syncytial virus, and human rhinovirus. Patients aged over 5 years displayed more diverse patterns, with varied correlations. The cases of fever were a strong indicator of respiratory viruses (human adenovirus, human parainfluenza viruses, and human rhinovirus) in children under 5 years old, while those over 5 years showed symptoms such as smell and taste disturbances. These findings emphasize the correlation between various symptoms and ARIs across different age groups and may help to improve syndromic surveillance systems.

Molecular characterization of RSV infections in elderly patients during the 2023/2024 season in the era of nirsevimab introduction.

RSV can cause severe infections in the elderly. Nirsevimab is a novel prophylactic monoclonal antibody, widely used in infants in France during the 2023/2024 season. It may select for resistant RSV variants that, if transmitted in the community, could compromise vaccine efficacy in the elderly. In this study, we analyzed RSV full-length genomes (68% RSV-A, 32% RSV-B) from 125 patients >60y during 2023/2024 season. Genetic diversity of RSV-F was low, with no resistance-associated substitutions (RASs) detected. While no RASs were identified, ongoing monitoring is essential to prevent the emergence of resistant variants that could affect vaccine efficacy in the elderly.

Early experience on universal prophylaxis in infants against RSV: Facts and expectations.

During the 2023-2024 season, nirsevimab significantly reduced the risk of bronchiolitis and confirmed RSV infections in primary care, hospital, and pediatric intensive care unit admissions among infants aged 0 to 11 months, even in a season with a high community RSV burden, particularly for older infants. These findings are very useful for public health authorities to continue to implement immunization campaigns against RSV in the coming seasons. Moreover, universal immunization against RSV represents a transformative step towards reducing the burden of RSV in infants. With promising evidence from recent published studies, the expectations for a reduction of RSV-associated hospitalizations, alongside the improvement of public health outcomes and an equitable access to these measures, are high. However, achieving these goals will require addressing challenges related to vaccine uptake, funding, and RSV surveillance to prompt detect resistances due to mutations of the virus. These interventions need to be integrated into public health strategies because they hold the potential to make a significant impact on infant's health worldwide.

Incidence of and Risk Factors for Subsequent Lower Respiratory Tract Infection Following an Infant RSV Hospitalization

Background/Objectives: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia in infants and the leading cause of infant hospitalization in the U.S. and worldwide. The risk of experiencing at least one other medically attended lower respiratory tract infection (MA LRTI) following an infant RSV hospitalization is less studied. Methods: We conducted a retrospective cohort study of infants who experienced an RSV hospitalization (index hospitalization) during infancy. The incidence rate of having a subsequent MA LRTI was reported. The association between a priori selected maternal and infant risk factors and subsequent MA LRTI was determined. Results: Of the 20,181 children who experienced an RSV hospitalization in infancy, 15% had at least one subsequent MA LRTI within the same RSV season. The incidence rates (95% confidence interval) of having a subsequent MA LRTI hospitalization, emergency department visit, or physician office visit in the same RSV season were 0.27 (0.26, 0.29), 0.16 (0.15, 0.17), and 0.46 (0.44, 0.48) per infant-year, respectively. Factors associated with an increased risk of subsequent MA-LRTI include younger maternal age, fewer years of maternal education, smoking during pregnancy, cesarean delivery, male infant sex, White race, siblings at home, urban residence, lower birth weight, lower gestational age, eligibility for and/or ever receiving palivizumab, longer birth hospitalization length of stay, longer index RSV hospitalization length of stay, intensive care unit admission for the index hospitalization, and summer-to-fall births. Conclusions: The burden of clinically significant subsequent MA-LRTI following an RSV hospitalization can be substantial. Our results highlight the importance of increasing accessible RSV LRTI preventive interventions.

Hospitalization cost estimates of respiratory syncytial virus and influenza infections in adults in Spain, 2016-2019.

Respiratory syncytial virus (RSV) is increasingly a recognized cause of severe respiratory infection among adults. This retrospective observational study compared the costs of RSV and influenza hospitalizations in adults aged ≥18years admitted to the Spanish National Healthcare System between 2016 and 2019. Mean costs per hospitalization episode were compared using a multivariable log-gamma generalized linear model adjusted by age, risk group and calendar year. Total annual hospitalization costs were estimated from population incidence rates (for RSV we used model-based rates reported in a published study due to the substantial under-ascertainment of cases) and the mean cost per episode. ICD-10 codes identified a total of 11,662 adults hospitalized with RSV and 79,319 with influenza. The mean length of stay was longer for RSV than for influenza in low-risk patients aged 60-79years, moderate-risk patients (those with chronic medical conditions) aged ≥50years and in high-risk (those with immunocompromising conditions) patients aged <80years. There were no differences in intensive care unit (ICU) admission (except for higher admission in high-risk RSV patients aged 70-79years), ICU stay or in-hospital case fatality rate. Mean costs per hospitalization episode were also similar: RSV €3870 (95% CI 3773-3942) vs influenza €3888 (95% CI 3836-3931). Total annual costs for RSV-attributable hospitalizations were estimated at M€194, twice than that of influenza (M€83). Annual costs increased by 11% over the study period for RSV and by 47% for influenza. In 2019, adults aged ≥60years and≥70years contributed 91% and 82%, respectively, of the total RSV-attributable hospitalization costs in adults. RSV has a significant economic burden to the Spanish National Healthcare System, likely greater than influenza. Efficacious RSV vaccines and antivirals have the potential for high public health impact.

Economic Impact of Respiratory Syncytial Virus Infections in Children Under 5 Years of Age Attending Primary Care in Italy: A Prospective Cohort Study in Two Regions.

Accurate cost estimates of respiratory syncytial virus (RSV) infections in primary care are limited, despite the majority of cases being managed in this setting. This study aims to estimate healthcare costs for children with RSV in primary care and the related costs of parental work absence. Children < 5 years of age with symptoms of acute respiratory infections were recruited via primary care paediatricians in two Italian regions for a prospective cohort study on the RSV burden in primary care, during the 2019/2020 winter. Healthcare utilization, medication use and parental work absence were assessed during a 14-day follow-up period. Average costs were estimated per RSV episode for the overall study population, as well as per age group. Two hundred ninety three children were recruited, of which 119 tested RSV positive (41%) and 109 were included. In total, 89% of RSV-positive children (97/109) had ≥ 1 repeat paediatrician visit(s), and 10% (11/109) visited the ED. The mean number of repeat visits was 3.8 (SD: 4.0) and the mean duration of work absence 4.0 days (SD: 5.0). Average costs per RSV episode were €730 (95% CI: €691-€771), with direct medical costs accounting for 25% (€183 [95% CI: €174-€191]) and indirect costs related to work absence for 75% (€547 [95% CI: €509-€587]). Costs associated with RSV infections in young children in primary care are considerable due to a substantial number of paediatrician visits and high rates of parental work absence. These costs are important to include in decision-making regarding the implementation of new RSV immunization strategies in national immunization programmes.

Estimating the cost-effectiveness of maternal respiratory syncytial virus (RSV) vaccination in Australia: A dynamic and economic modelling analysis.

Respiratory syncytial virus (RSV) is a major cause of respiratory illness, with younger infants at greatest risk of hospitalisation. With the recent approval of a maternal RSV vaccine in Australia, it is timely to evaluate its potential costs and health benefits in Australia. We applied an integrated dynamic and economic evaluation model to estimate specific outcomes of RSV disease and the cost-effectiveness of a year-round maternal RSV vaccination program in Australia. Cost-effectiveness was estimated using the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained. From a healthcare system perspective, the maternal vaccination program was estimated to be cost-effective at a vaccine price less than approximately 120 Australian dollars ($AU), assuming a willingness-to-pay (WTP) threshold of $AU 50,000/QALY gained. Most of the estimated cost-savings were from preventing RSV hospitalisations in infants aged <6months. However, while 82% of the cost-savings were from preventing RSV hospitalisations in infants aged <6months, only about 25% of the QALY gains were in this age group. The majority of the other QALY gains came via herd effects from prevention of death in older adults and to a lesser extent, prevention of nonmedically-attended illness in older teens and adults. When predicted cost-savings and QALY gains in those ≥6months of age were excluded, the vaccine price required to meet the assumed WTP threshold fell to $AU 63. A maternal RSV vaccination program in Australia could provide value for money by reducing hospitalisations and associated costs among infants aged <6months, depending on the vaccine price. We have provided evidence that herd effects beyond the target population may be an important consideration in assessing cost-effectiveness of maternal RSV vaccination.