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Objectives Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. We assessed severe clinical outcomes among hospitalized adults that were associated with RSV infections. Methods We performed a nested retrospective study in 3 New York City hospitals during 2 respiratory viral seasons, October 2017–April 2018 and October 2018–April 2019, to determine the proportion of patients with laboratory-confirmed RSV infection who experienced severe outcomes defined as intensive care unit (ICU) admission, mechanical ventilation, and/or death. We assessed factors associated with these severe outcomes and explored the effect of RSV-associated hospitalizations on changes in the living situations of surviving patients. Results Of the 403 patients studied (median age, 69 years), 119 (29.5%) were aged ≥80. Severe outcomes occurred in 19.1% of patients, including ICU admissions (16.4%), mechanical ventilation (12.4%), and/or death (6.7%). Patients admitted from residential living facilities had a 4.43 times higher likelihood of severe RSV infection compared with patients who were living in the community with or without assistance from family or home health aides. At discharge, 56 (15.1%) patients required a higher level of care than at admission. Conclusions RSV infection was associated with severe outcomes in adults. Living in a residential facility at admission was a risk factor for severe outcomes and could be a proxy for frailty rather than an independent risk factor. Our data support the development of prevention strategies for RSV infection in older populations, especially older adults living in residential living facilities.

Elucidating the infection dynamics that lead to severe respiratory syncytial virus (RSV) pneumonia and hospitalization among young children are critical. We explored the role of infection parity as well as age in months for RSV-associated hospitalization among young children in Japan.We used a sequential transmission catalytic model to capture the transmission mechanisms of RSV among infants in an endemic state. We investigated data on the age-dependent seroprevalence and incidence rate of hospitalization in Japan, and jointly estimated the age-specific risk of hospitalization during primary RSV infection and relative risk of hospitalization during secondary infection in children aged5 years.The estimated risk of hospitalization with primary infection was 0.08 (95% CI: 0.05-0.14) in infants aged 0-2 months. The estimated relative risk of hospitalization owing to secondary infection was 0.18 (95% CI: 0.01-2.04).Our simple models successfully captured the infection dynamics of RSV among young children in Japan. The age group of early infancy may be most vulnerable to infection and hospitalization, offering key insights into future vaccinations. The burden of hospitalization from secondary infection may be less important in young children.

Interactions between respiratory viruses during infection affect transmission dynamics and clinical outcomes. To identify and characterize virus-virus interactions at the cellular level, we coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy, live-cell imaging, scanning electron microscopy and cryo-electron tomography revealed extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs). We found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralizing antibodies and infect and spread among cells lacking IAV receptors. Finally, we show that IAV and RSV coinfection in primary cells of the bronchial epithelium results in viral proteins from both viruses co-localizing at the apical cell surface. Our observations define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and enabling immune evasion.

Background The interplay among respiratory syncytial virus (RSV) loads, mucosal interferons (IFN), and disease severity in RSV-infected children is poorly understood. Methods Children 6–24 months) and multivariable analyses performed to identify predictors of disease severity. Results In 2015–2019 we enrolled 219 RSV-infected children (78 outpatients; 141 inpatients) and 34 healthy controls. Type I, II, and III IFN concentrations were higher in children aged >6 versus 0–6 months and, like CXCL10, they were higher in outpatients than inpatients and correlated with RSV loads (P < .05). Higher IL6 concentrations increased the odds of hospitalization (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.07–5.36) only in children >6 months, while higher IFN-λ2/3 concentrations had the opposite effect irrespective of age (OR, 0.38; 95% CI, .15–.86). Likewise, higher CXCL10 concentrations decreased the odds of hospitalization (OR, 0.21; 95% CI, .08–.48), oxygen administration (OR, 0.42; 95% CI, .21–.80),PICU admission (OR, 0.39; 95% CI, .20–.73), and prolonged hospitalization (OR, 0.57; 95% CI, .32–.98) irrespective of age. Conclusions Children with milder RSV infection and those aged >6 months had higher concentrations of mucosal IFNs, suggesting that maturation of mucosal IFN responses are associated with protection against severe RSV disease.

Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide. Until now, there are no licenced vaccines or effective antiviral drugs against RSV infections. In our previous work, we found 2-((1H-indol-3-yl)thio/sulfinyl)-N-pheny acetamide derivatives (4-49 C and 1-HB-63) being a novel inhibitor against RSV

Respiratory syncytial virus (RSV) causes lower respiratory tract infections and bronchiolitis, mainly affecting children under 2 years of age and immunocompromised patients. Currently, there are no available vaccines or efficient pharmacological treatments against RSV. In recent years, tremendous efforts have been directed to understand the pathological mechanisms of the disease and generate a vaccine against RSV. Although RSV is highly infectious, not all the patients who get infected develop bronchiolitis and severe disease. Through various sequencing studies, single nucleotide polymorphisms (SNPs) have been discovered in diverse receptors, cytokines, and transcriptional regulators with crucial role in the activation of the innate immune response, which is implicated in the susceptibility to develop or protect from severe forms of the infection. In this review, we highlighted how variations in the key genes affect the development of innate immune response against RSV. This data would provide crucial information about the mechanisms of viral infection, and in the future, could help in generation of new strategies for vaccine development or generation of the pharmacological treatments.

BACKGROUND: Respiratory syncytial virus (RSV) causes severe respiratory illnesses in infants and older adults. Older adults are frequently hospitalized with RSV illness and may experience loss of function. This study evaluated longitudinal changes in function associated with RSV hospitalization in older adults. METHODS: Adults ≥60 years hospitalized with laboratory‐confirmed RSV were enrolled (N = 302). Demographics and comorbidities were collected. Functional status was assessed 2 weeks pre‐hospitalization by recall, at enrollment, hospital discharge and 2, 4, and 6 months post‐discharge using the Lawton–Brody Instrumental Activities of Daily Living (IADL) (scale 0–8) and Barthel ADL Index (scale 0–100). RESULTS: RSV‐associated hospitalization resulted in acute functional loss. Median IADL (5 vs. 3, p

Ninety percent of children are infected with respiratory syncytial virus (RSV) within their first two years of life. RSV is the main cause behind hospitalization of infants with lower respiratory tract infections. A new monoclonal antibody (mAb) immunization may prevent RSV in all infants. This cross-national study aimed to examine parental knowledge about RSV and attitudes to such RSV immunization.Based on a literature study, a questionnaire was designed and applied in a survey carried out in China, France, Germany, Italy, Japan, Spain, the UK, and the US. Eligible respondents were expecting their first baby or parents of children24 months old who were open to vaccination.Parental acceptance of immunizations relies on perceptions of the preventable disease. In 5627 parents, only 35% reported basic or good level of knowledge about RSV. Recommendation from health care professionals and inclusion in immunization programs were crucial to their acceptance of RSV immunization. If recommended and informed about its efficacy and safety, most parents would accept RSV mAb immunization for their infants.Infant RSV infections are highly prevalent, yet parental awareness of RSV is poor. Country variations call for targeted communication about RSV and immunization.Almost all children (90%) are infected with respiratory syncytial virus (RSV) before the age of two. Most cases of RSV are mild, but RSV remains the main cause behind hospitalization of infants with lung infections, such as bronchiolitis and pneumonia. A new immunization with monoclonal antibodies (mAbs) is currently being developed to prevent RSV in infants. While traditional vaccines act to mobilize a person’s own production of antibodies to fight a virus, immunization with mAbs means that antibodies are given directly. We know that parents’ attitudes to childhood vaccination depend on their views on childhood diseases and vaccination in general. Therefore, we wanted to examine what parents know about RSV. How widespread and severe do parents think RSV infection is? Would they like their infants to receive RSV immunization? To answer these questions, we carried out a survey in eight Western and Asian countries. More than 5000 people who were either expecting their first baby or already parents of under two-year-olds answered the questionnaire. Their responses showed that awareness of RSV was poor as two-thirds of parents had never heard of RSV or knew only the name. Once exposed to information about a hypothetical immunization against RSV disease, the immunization was considered beneficial; however, recommendation from health care professionals and inclusion in immunization programs were crucial to the parents’ ultimate acceptance of RSV immunization. If recommended and well informed about its safety and efficacy, most parents would accept mAb immunization against RSV for their infants.

Background Death certificate data can improve our understanding of the mortality burden associated with respiratory syncytial virus (RSV) and influenza. Methods We used International Classification of Diseases, Tenth Revision codes listed on death certificates to characterize deaths from 1999 to 2018 as RSV, influenza, and unspecified bronchiolitis. We described the distribution of each cause of death by age, sex, race/ethnicity, place of death, and contributing causes of death. Results Over the 20-year study period, RSV, bronchiolitis, and influenza were listed as the underlying causes of death on 932, 1046, and 52 293 death certificates, respectively. Children Conclusions Thorough reporting on death certificates is an important public health goal, especially as new therapeutics become available. Infants had higher odds of dying out of hospital from respiratory pathogens compared to other causes, and race/ethnicity alone did not explain this disparity.

Background Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in United States infants aged Methods National (Nationwide) Inpatient Sample and National Emergency Department (ED) Sample data (2011–2019) were used to report RSV hospitalization (RSVH), bronchiolitis hospitalization (BH), and ED visit counts, percentage of total hospitalizations/visits, and rates per 1000 live births along with inpatient mortality, mechanical ventilation (MV), and total charges (2020 US dollars). Results Average annual RSVH and RSV ED visits were 56 927 (range, 43 845–66 155) and 131 999 (range, 89 809–177 680), respectively. RSVH rates remained constant over time (P = .5), whereas ED visit rates increased (P = .004). From 2011 through 2019, Medicaid infants had the highest average rates (RSVH: 22.3 [95% confidence interval {CI}, 21.5–23.1] per 1000; ED visits: 55.9 [95% CI, 52.4–59.4] per 1000) compared to infants with private or other/unknown insurance (RSVH: P Conclusions This study highlights the importance of ensuring access to RSV preventive measures for all infants.

Background A systematic literature review was conducted to summarize the mortality (overall and by disease severity factors) of US infants and children aged Methods Comprehensive, systematic literature searches were conducted; articles were screened using prespecified eligibility criteria. A standard risk of bias tool was used to evaluate studies. Mortality was extracted as the rate per 100 000 or the case fatality ratio (CFR; proportion of deaths among RSV/ACB cases). Results Among 42 included studies, 36 evaluated inpatient deaths; 10 used nationally representative populations updated through 2013, and only 2 included late-preterm/full-term otherwise healthy infants and children. The RSV/ACB definition varied across studies (multiple International Classification of Diseases [ICD] codes; laboratory confirmation); no study reported systematic testing for RSV. No studies reported RSV mortality rates, while 3 studies provided ACB mortality rates (0.57–9.4 per 100 000). CFRs ranged from 0% to 1.7% for RSV (n = 15) and from 0% to 0.17% for ACB (n = 6); higher CFRs were reported among premature, intensive care unit-admitted, and publicly insured infants and children. Conclusions RSV mortality reported among US infants and children is variable. Current, nationally representative estimates are needed for otherwise healthy, late-preterm to full-term infants and children.

Background Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States. Methods We performed a systematic literature review of 10 key databases to identify studies published between 1 January 2014 and 2 August 2021 that reported RSV-related costs in US children aged 0–59 months. Costs were extracted and a systematic analysis was performed. Results Seventeen studies were included. Although an RSV hospitalization (RSVH) of an extremely premature infant costs 5.6 times that of a full-term infant ($10 214), full-term infants accounted for 82% of RSVHs and 70% of RSVH costs. Medicaid-insured infants were 91% more likely than commercially insured infants to be hospitalized for RSV treatment in their first year of life. Medicaid financed 61% of infant RSVHs. Paying 32% less per hospitalization than commercial insurance, Medicaid paid 51% of infant RSVH costs. Infants’ RSV treatment costs $709.6 million annually, representing $187 per overall birth and $227 per publicly funded birth. Conclusions Public sources pay for more than half of infants’ RSV medical costs, constituting the highest rate of RSVHs and the highest expenditure per birth. Full-term infants are the predominant source of infant RSVHs and costs.

The target populations and financing mechanisms for a new health technology may affect health inequalities in access and impact. We projected the distributional consequences of introducing nirsevimab for prevention of respiratory syncytial virus in a US birth cohort of infants through alternative reimbursement pathway scenarios. Using the RSV immunization impact model, we estimated that a vaccine-like reimbursement pathway would cover 32% more infants than a pharmaceutical pathway. The vaccine pathway would avert 30% more hospitalizations and 39% more emergency room visits overall, and 44% and 44%, respectively, in publicly insured infants. The vaccine pathway would benefit infants from poorer households.

Background The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged Methods We systematically reviewed studies of RSV and bronchiolitis published 2000–2021 (data years, 1979–2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools. Results We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6–11 months in 2006 to 50.1 per 1000 per year among infants aged 0–2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0–22.7 per 1000 in 1997–1999 and 1997–2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non–high-risk infants in 1997-2012. Conclusions Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.

BACKGROUND: The Pediatric Respiratory Syncytial Virus Electronic Severity and Outcome Rating System (PRESORS) was developed to assess the severity of respiratory syncytial virus (RSV) infection in children. Because young children cannot report how they feel or function, ratings are based on observations by the child's caregiver (Observer‐Reported Outcome questionnaire [ObsRO]) and clinician (Clinician‐Reported Outcome questionnaire [ClinRO]). This prospective study aimed to evaluate the psychometric properties of the PRESORS. METHODS: The PRESORS version 6 ObsRO and ClinRO were evaluated in children with RSV infection requiring hospitalization in centers in the United States, Argentina, and Chile. Assessments were performed from days 1 to 7 by the child's caregiver and clinician. To assess inter‐rater reliability, two clinicians independently performed the ClinRO near in time. RESULTS: A total of 124 children aged ≤36 months were enrolled (mean age, 8 months). Factor analysis demonstrated that RSV severity consists of two dimensions, respiratory signs and illness behavior, and that these dimensions were consistent over time. The inter‐rater reliability for the ClinRO was 0.66 (95% confidence interval [CI], 0.55–0.75) but improved to 0.79 (95% CI, 0.71–0.86) after removing one outlying site, suggesting that quantifying RSV severity is not trivial, even using qualified raters, but that an adequate inter‐rater reliability is achievable with the PRESORS through adequate training. ClinRO and ObsRO displayed acceptable internal consistency and acceptable convergent validity with the Respiratory Syncytial Virus Network Scale, global impression scores, and key hospital characteristics. CONCLUSIONS: The PRESORS is relevant and appropriate for assessing the severity of RSV infection in infants requiring hospitalization.

Upper respiratory illnesses due to viruses are the most common reason for pediatric emergency department (ED) visits in the United States. We explored the clinical characteristics, hospitalization risk, and symptom duration of children in an ED setting by respiratory pathogen including coinfections. A retrospective analysis was conducted from a randomized controlled trial evaluating a rapid molecular pathogen panel among 931 children 1 month to 18 years of age with acute respiratory illness. We assessed hospitalization risk by pathogen using multivariable Poisson regression with robust variance. Symptom duration was assessed using multivariable Cox proportional hazards models. Among 931 children, 702 (75%) were aged 0-5 years and 797 (85%) tested positive for a respiratory pathogen. Children with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human rhinovirus/enterovirus (HRV/EV) had higher hospitalization risk compared with influenza (adjusted risk ratio [aRR]: 2.95, 95% confidence interval [CI]: 1.17-7.45; 3.56, 95% CI: 1.05-12.02; aRR: 2.58, 95% CI: 1.05-6.35, respectively). Children with RSV, parainfluenza and atypical bacterial pathogens had longer illness duration compared with influenza (adjusted hazards ratio [aHR]: 2.16 95% CI: 1.41-3.29; aHR: 1.67, 95% CI:1.06-2.64; aHR: 2.60 95% CI: 1.30-5.19, respectively). Children with RSV, hMPV, and atypical bacterial pathogens had higher illness severity and duration compared with other respiratory pathogens. Coinfection was not associated with increased illness severity.

Human respiratory syncytial virus (HRSV) is a leading cause worldwide of severe respiratory illness in infants and the elderly. The ideal HRSV vaccine should induce a systemic immune response, especially mucosal immunity. In this study, mice were immunized twice with F protein combined with CpG adjuvant to compare the safety and efficacy of 4 immunization routes, including intranasal primed/intramuscular boosted immunization (CpG + F/in+im), intramuscular primed/intranasal boosted immunization (CpG + F/im+in), intramuscular primed/intramuscular boosted immunization (CpG + F/im + im) and intranasal primed/intranasal boosted immunization (CpG + F/in+in). Compared with the control group (CpG/in+im, CpG/im+in, CpG/im + im and CpG/in+in), all 4 immunization routes induced a high titer of neutralizing antibodies and a strong cellular immune response. Mice in the CpG + F/in+in group induced the highest antibody neutralization titer, and IgA antibody in bronchoalveolar lavage fluid (BALF) was the highest. The copy of HRSVs in the lung decreased by approximately 3 log10. As seen from the IgG1/IgG2a and IFN-γ/IL-4-secreting lymphocyte ratios, compared with the mice in the CpG + F/im + im group, mice in the CpG + F/in+in group induced Th1-baised humoral and cellular immune responses and significantly reduced lung pathological injury. In conclusion, among the 4 immunization routes, the safety and efficacy induced by the mice in the CpG + F/in+in group were the best. We can conclude that intranasal immunization is superior to intramuscular immunization using F protein with CpG adjuvant as vaccine candidates.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children. Axl, a TAM family receptor tyrosine kinase, has been demonstrated to be a receptor mediating enveloped virus infection. Here we show that Axl functions as a suppressor of antiviral response during RSV infection. Knockdown of Axl expression in human cells resulted in cell resistance to RSV infection, although the treatment did not significantly affect RSV binding or cell entry. Mice deficient in

Respiratory syncytial virus (RSV)-associated diseases have caused an estimated 1.8 million hospital admissions and 40,000 deaths among children. RSV can cause lower respiratory tract infections (LRTIs) in all age groups, adults with comorbidities, and immunocompromised patients. The aim was to summarize the evidence concerning efficacy and safety of ribavirin in subjects diagnosed with RSV associated with LRTI.A systematic review and meta-analysis were performed. Eligible studies were observational ( 10 subjects) and randomized-controlled trials of subjects with aerosol/oral ribavirin for RSV-LRTI. Comparator was supportive care or placebo. Systematic search on PubMed, Cochrane Library, and Web of Science databases was conducted between January 2001 and January 2022. PROSPERO register number: CRD42022308147.After retrieving 907 studies, 10 observational studies and 1 randomized controlled trial were included (4/11 high quality of evidence). Seven studies included subjects with haematological malignancy/stem cell transplant, two lung transplants, and two healthy individuals. A total of 788 subjects diagnosed with RSV infection were included; 14.3% of them presented with only LRTI. Among 445 subjects treated with ribavirin, 195 (43.8%) received an aerosolized formulation. Pooled meta-analysis showed no differences in mortality [risk ratio (RR): 0.63; 95% confidence interval (CI): 0.28-1.42] in all subjects treated with aerosol/oral ribavirin compared to supportive care. In subgroup analysis, mortality was significantly lower in haematological subjects (RR: 0.32; 95% CI: 0.14-0.71), but did not differ significantly in lung transplant recipients (RR: 0.89; 95% CI 0.31-2.56). Oral ribavirin (vs. supportive care) was associated with increased viral clearance (RR: 2.60; 95% CI: 1.35-4.99). Seventeen adverse events were reported among 119 subjects, but none were severe.Ribavirin should be considered for treatment of RSV-LRTI in haematological subjects. There is a lack of evidence to support its use in lung transplant recipients. Oral formulation appears to be an easier, safe, and cost-effective alternative to aerosolized ribavirin. Further advances needs to focus on newer antivirals.

Background This study describes leading causes of hospitalization, including respiratory syncytial virus (RSV), in United States infants ( Methods Within the National (Nationwide) Inpatient Sample (NIS) data, hospitalizations were determined by primary diagnosis using International Classification of Diseases, Ninth or Tenth Revision codes. RSV was defined as 079.6, 466.11, 480.1, B97.4, J12.1, J20.5, or J21.0. Bronchiolitis was defined as 466.19, J21.8, or J21.9. Leading causes overall and by sociodemographic variables were identified. The Kids’ Inpatient Database (KID) was used for confirmatory analyses. Results Acute bronchiolitis due to RSV (code 466.11 or J21.0) was the leading primary diagnosis, accounting for 9.6% (95% confidence interval [CI], 9.4%–9.9%) and 9.3% (95% CI, 9.0%–9.6%) of total infant hospitalizations from January 2009 through September 2015 and October 2015 through December 2019, respectively; it was the leading primary diagnosis in every year accounting for >10% of total infant hospitalizations from December through March, reaching >15% in January–February. From 2009 through 2011, acute bronchiolitis due to RSV was the leading primary diagnosis in every birth month. Acute bronchiolitis due to RSV was the leading cause among all races/ethnicities, except Asian/Pacific Islanders, and all insurance payer groups. KID analyses confirmed these results. Conclusions Acute bronchiolitis due to RSV is the leading cause of US infant hospitalizations.

To evaluate the impact of immunoprophylaxis with palivizumab in preterm infants less than 35 weeks in terms of hospitalization rate, intensive care unit requirement, and mortality.A prospective cohort study was conducted at six Colombian hospitals. Preterm infants less than 35 weeks who received at least one dose of palivizumab during the first 6 months of life were included. The primary outcome was the hospitalization rate related to respiratory syncytial virus (RSV) infection.A total of 222 newborns participated in the study; 204 (91.8%) completed the 6-month follow-up, and three died during the study. 88.7% received a second dose of palivizumab, 79.7% a third, 34.7% a fourth, and 25.2% a fifth. The nonadjusted incidence rate of RSV infection was 2.4%, and the overall RSV-positive hospitalization rate was 1.9%. The proportion of patients that required Neonatal Intensive Care Unit (NICU) and mechanical ventilation in relation to RSV infection was 1.4%. Discharge with home oxygen, pulmonary dysplasia, and being younger than 6 months were significantly associated with respiratory infection. Furthermore, exposition to cigarette smoke was the only factor associated with increased risk of hospitalization. The group that required hospitalization received fewer doses of palivizumab (p = 0.049). No discontinuation of treatment due to adverse events were reported. No death was judged to be related to palivizumab.The hospitalization rate and the need for NICU admission were lower than those reported in the literature. In this real-life setting, palivizumab appears to be effective in preventing serious cases of RSV infection.

Objectives: Year-to-year variation in respiratory viruses may result in lower attack rates than expected. We aimed to illustrate the impact of year-to-year variation in attack rates on the likelihood of demonstrating vaccine efficacy (VE).Study Design and Setting: We considered an individually randomized maternal vaccine trial against respiratory syncytial virus (RSV)-associated hospitalizations. For 10 RSV-associated hospitalizations per 1,000 infants, sample size to have 80% power for true VE of 50% and 70% was 9,846 and 4,424 participants. We reported power to show VE for varying attack rates, selected to reflect realistic year-to-year variation using observational studies. Eight scenarios including varying number of countries and seasons were developed to assess the influence of these trial parameters.Results: Including up to three seasons decreased the width of the interquartile range for power. Including more seasons concentrated statistical power closer to 80%. Least powered trials had higher statistical power with more seasons. In all scenarios, at least half of the trials had Conclusion: Year-to-year variation in RSV attack rates should be accounted for during trial design. Mitigation strategies include recruiting over more seasons, or adaptive trial designs.

Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited.We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations inlt;5-year-olds were used as proxies for relative weekly viral activity.From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) inlt;5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively.RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

Little RSV activity was observed during the first expected RSV season since the COVID-19 pandemic. Multiple countries later experienced out-of-season RSV resurgences, yet their association with non-pharmaceutical interventions (NPIs) is unclear. This study aimed to describe the changes in RSV epidemiology during the COVID-19 pandemic and to estimate the association between individual NPIs and the RSV resurgences.RSV activity from Week (W)12-2020 to W44-2021 was compared with three pre-pandemic seasons using RSV surveillance data from Brazil, Canada, Chile, France, Israel, Japan, South Africa, South Korea, Taiwan, the Netherlands and the United States. Changes in nine NPIs within 10 weeks before RSV resurgences were described. Associations between NPIs and RSV activity were assessed with linear mixed models. Adherence to NPIs was not taken into account.Average delay of the first RSV season during the COVID-19 pandemic was 39 weeks (range: 13-88 weeks). Although the delay was40 weeks in six countries, a missed RSV season was observed in Brazil, Chile, Japan, Canada and South Korea. School closures, workplace closures, and stay-at-home requirements were most commonly downgraded before an RSV resurgence. Reopening schools and lifting stay-at-home requirements were associated with increases of 1.31% (p = 0.04) and 2.27% (p = 0.06) in the deviation from expected RSV activity.The first RSV season during the COVID-19 pandemic was delayed in the 11 countries included. Reopening of schools was consistently associated with increased RSV activity. As NPIs were often changed concomitantly, the association between RSV activity and school closures may be partly attributed to other NPIs.

Respiratory Syncytial Virus (RSV) imposes a large disease burden on a global level. Public awareness of RSV is important to support preventive interventions. In this study, Google Trends and a social listening tool, Brand24, were compared for measuring changes in public awareness levels of RSV. Google Trends is recommended for future research, as it is more sensitive, cost-free and open access.

BackgroundThe true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life.MethodsThis prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods.ResultsOf 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval [CI], 5.88–9.08), 5.50 (95% CI, 4.21–7.07), and 2.87 (95% CI, 2.18–3.70) cases/100 person-years in children aged 0–5, 6–11, and 12–23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0–5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0–2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs.ConclusionsA substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most.Clinical Trials Registration. NCT01995175.

During the COVID-19 pandemic, sample pooling has proven an effective strategy to overcome the limitations of reagent shortages and expand laboratory testing capacity. The inclusion of influenza and respiratory syncytial virus (RSV) in a multiplex tandem PCR platform with SARS-CoV-2 provides useful diagnostic and infection control information. This study aimed to evaluate the performance of the influenza and RSV targets in the AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay, including the effect of pooling samples on target detection. RSV target detection in clinical samples was compared to the Cepheid Xpert Xpress Flu/RSV assay as a reference standard. Samples were then tested in pools of four and detection rates were compared. Owing to the unavailability of clinical samples for influenza, only the effect of sample pooling on simulated samples was evaluated for these targets. RSV was detected in neat clinical samples with a positive percent agreement (PPA) of 100% and negative percent agreement (NPA) of 99.5% compared to the reference standard, demonstrating 99.7% agreement. This study demonstrates that sample pooling by four increases the average Ct value by 2.24, 2.29, 2.20 and 1.91 cycles for the target's influenza A, influenza A typing, influenza B and RSV, respectively. The commercial AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay was able to detect influenza and RSV at an intermediate concentration within the limit of detection of the assay. Further studies to explore the applicability of sample pooling at the lower limit of detection of the assay is needed. Nevertheless, sample pooling has shown to be a viable strategy to increase testing throughput and reduce reagent usage. In addition, the multiplexed platform targeting various respiratory viruses assists with public health and infection control responses, clinical care, and patient management.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory infection, and therefore, a major threat to global health. This study determined the epidemiological and molecular characteristics of RSV among cases of influenza-like illness (ILI) and severe acute respiratory infection (SARI) among children in the Philippines.The study included archived nasopharyngeal swab and oropharyngeal swab samples collected from patients under the age of five who are presented with ILI or SARI for the period of 2006-2016. Swabs were examined for RSV subgroup by multiplex real-time qRT-PCR. Partial genome sequencing and phylogenetic analyses of the second hypervariable region (HVR) of the G gene were used to determine the genotype of RSV isolates.A total of 1036 representative samples from all sites were selected and tested. Of these samples, 122 were RSV-positive at 11.8% prevalence rate, and 58.2% (71/122) were classified as RSV-A. Six genotypes were identified, which include NA1 (27/122, 22.1%), ON1 (5/122, 4.1%), GA2 (1/122, 0.8%), and GA5 (1/122, 0.8%) for RSV-A; and BA2 (13/122, 10.7%) and BA9 (1/122, 0.8%) for RSV-B. Most RSV-related cases were significantly associated with clinical characteristics such as runny nose (88.1% RSV vs. 11.9% non-RSV: p value = 0.021), pneumonia (80.6% RSV vs. 19.4% non-RSV; p value = 0.015), and bronchitis (71.7% RSV vs. 28.3% non-RSV; p value 0.001). Increased RSV-related cases were observed among children below 24 months old.The RSV trend and genetic variability in the Philippines resembles a similar pattern of transmission globally.

Respiratory viral infections account for a large percentage of global disease and death. Respiratory syncytial virus is a seasonal virus affecting immunologically vulnerable populations, such as preterm newborns and young infants; however, its epidemiology has changed drastically during the coronavirus disease 2019 pandemic. In this perspective, we discuss the implications of coronavirus disease 2019 on respiratory syncytial virus seasonality patterns and mitigation efforts, as well as the urgent need for vaccination as a preventive tool.

Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection (ARI), with high morbidity and mortality worldwide. RSV costing and burden estimates can highlight the potential benefits of future vaccination programs and are essential for economic evaluations.We aimed to determine RSV healthcare costs across age groups and the overall disease burden of medically attended RSV in Canada.We conducted a retrospective case-control study to estimate the attributable healthcare costs per RSV case in Alberta. We used two case definitions to capture diversity in case severity: laboratory-confirmed RSV and ARI attributable to RSV. Matching occurred on five criteria: (1) age, (2) urban/rural status, (3) sex, (4) prematurity and (5) Charlson Comorbidity Index score. We calculated the age-specific burden of medically attended RSV in Canada from 2010 to 2019 by multiplying the weekly age-specific incidence of medically attended ARI with the RSV positivity rate.Costs per laboratory-confirmed RSV case were (in Canadian dollars [CAD], year 2020 values) $CAD12,713 and 40,028 in the first 30 and 365 days following diagnosis, respectively, whereas a case of ARI potentially attributable to RSV cost $CAD316 and 915, in 30 and 365 days, respectively. Older (aged ≥ 65 years) and younger (aged 90 days) age groups had the highest case costs. The average medically attended RSV incidence rate across nine seasons was 1743 cases per 100,000 people per year.RSV is a common and expensive infection at the extremes of life, and the development of immunization programs targeting older and younger ages may be important for the reduction of RSV burden and cost.

Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models. C57BL/6J mice at 8 days old were exposed to RSV 2 times with a 4-week interval. A subset of RSV-infected mice was subsequently treated with Cd at a low dose in drinking water (RSV infection at infant age [RSVinf]+Cd) for 16 weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSVinf+Cd group than other groups, implying that low-dose Cd following early-life RSV infection enhanced lung inflammation. Moreover, histopathology data showed that inflammatory cells and thickening of the alveolar walls as a profibrotic signature were evident in RSVinf+Cd. The metabolomics data revealed that RSVinf+Cd-caused metabolic disruption in histamine and histidine, vitamin D and urea cycle, and pyrimidine pathway accompanying with mechanistic target of rapamycin complex-1 activation. Taken together, our study demonstrates for the first time that cumulative Cd exposure following early-life RSV infection has a significant impact on subsequent inflammation and lung metabolism. Thus, early-life respiratory infection may reprogram metabolism and potentiate Cd toxicity, enhance inflammation, and cause fibrosis later in life.

Bronchiolitis is the most frequent cause of hospitalization in infants younger than 1 year of age. We sought to evaluate the correlation between lymphocyte count and clinical manifestation in infants hospitalized with bronchiolitis.We performed a retrospective cohort study evaluating 1297 children hospitalized for bronchiolitis from 2004 to 2019. A nasal washing was tested for 14 respiratory viruses by PCR. A clinical severity score, ranging 0-8, was assigned at hospital admission. History and clinical course were recorded for each infant. Patients were divided in 3 groups according to lymphocyte count tertiles. Parents of enrolled patients have been phoned annually over 5 years to evaluate respiratory sequelae.A total of 433 children had 2914.2 ± 745.5/mmInfants with low lymphocyte count are more likely to have a worse clinical course of bronchiolitis.

Based on our national outpatient sentinel surveillance, we have developed a novel approach to determine respiratory syncytial virus (RSV) epidemic seasons in Germany by using RSV positivity rate and its lower limit of 95% confidence interval. This method was evaluated retrospectively on nine RSV seasons, and it is also well-suited to describe off-season circulation of RSV in near real time as observed for seasons 2020/21 and 2021/22 during the COVID-19 pandemic. Prospective application is of crucial importance to enable timely actions for health service delivery and prevention.

Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain.In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios.This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios.RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

Influenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.HARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017-2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post-discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, chronic heart or renal disease, chronic obstructive pulmonary disease, or asthma), and MRU were summarized descriptively.The US cohort included 280 influenza-positive and 120 RSV-positive patients. RSV patients were older (mean: 63.1 vs. 59.7 years) and a higher proportion had CRFs (87.5% vs. 81.4%). Among those with CRFs (influenza, n = 153; RSV, n = 99), RSV patients required longer hospitalizations (median length of stay: 4.5 days) and a greater proportion (79.8%) required oxygen supplementation during hospitalization compared with influenza patients (4.0 days and 59.5%, respectively). At 3 months post-discharge, a greater proportion of RSV patients with CRFs reported use of antibiotics, antitussives, bronchodilators, and inhaled and systemic steroids versus those with influenza and CRFs. Many patients with CRFs reported hospital readmission at 3 months post-discharge (RSV: 13.4%; influenza: 11.9%).MRU during and post-hospitalization due to RSV in adults is similar to or greater than that of influenza. Enhanced RSV surveillance and preventive and therapeutic interventions are needed.

Background Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood. Methods From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants Results Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4–7.5), 19.8 (95% CI, 18.9–20.8), and 6.2 (95% CI, 5.7–6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among Conclusions These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.

Background Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection. Methods We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who developed recurrent RSV infection. We analyzed gene expression profiles and interleukin (IL)-6 production by patient peripheral blood mononuclear cells in response to RSV pre- and post-fusion (F) protein. We generated CD14-deficient human nasal epithelial cells cultured at air-liquid interface (HNEC-ALI) of patient-derived cells and after CRISPR-based gene editing of control cells. We analyzed viral replication upon RSV infection. Results Sanger sequencing revealed a homozygous single-nucleotide deletion in CD14, resulting in absence of the CD14 protein in the index patient. In vitro, viral replication was similar in wild-type and CD14−/− HNEC-ALI. Loss of immune cell CD14 led to impaired cytokine and chemokine responses to RSV pre- and post-F protein, characterized by absence of IL-6 production. Conclusions We report an association of recurrent RSV bronchiolitis with a loss of CD14 function in immune cells. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein without a change in viral replication.

Background Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in children (≤5 years of age); limited data compare burden by age. Methods This single-center retrospective study included children (≤5 years of age) hospitalized for >24 hours with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed RSV infection (2015–2018). Hospital length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, supplemental oxygen, and medication use were assessed. Multivariate logistic regression analyses identified predictors of hospital LOS >5 days. Results Three hundred twelve patients had RSV infection (ages 0 to Conclusions RSV causes substantial burden in hospitalized children (≤5 years), particularly preterm infants and those aged

Acute viral bronchiolitis is the major cause of hospital admissions in children under 2 years of age, and respiratory syncytial virus (RSV) can be responsible for up to 80% of these infections. We aimed to describe RSV dynamics among hospitalized children with bronchiolitis. Upper respiratory samples of 101 hospitalized patients were collected and submitted to RSV detection by a quantitative real-time RT-PCR to assess viral load (Log(10) RNA copies/mL). Seventy-two patients were positive for RSV infection, of which 38 (52.7%) could be followed up until RSV was no longer detected. The first RSV RT-qPCR was carried out on average on the 5th day of symptom onset. Thirty-six patients (94.7%) were still shedding RSV after 7 days, and 9 (23.6%) after 14 days of symptoms onset. Only 2 patients (5.2%) were still shedding RSV after 21 days. Only 7 of the followed patients (18.9%) were submitted to intubation. There was no difference between the viral load of the first collected sample and the viral persistence of patients with comorbidities, who needed intensive care unit and who needed intubation. These data could help understand RSV dynamics and future studies and treatments to come.

Background Respiratory syncytial virus (RSV) and influenza virus infections result in a considerable mortality and morbidity among the aging population globally. Influenza vaccination for older adults before the seasonal influenza epidemic has been evaluated to be cost-effective in many countries. Interventions against RSV in older adults are in the pipeline, and evaluating their cost-effectiveness is crucial for decision making. To inform such evaluations, our aim was to estimate average costs and health-related quality of life (HRQoL) in older adults with RSV and influenza infection. Methods The European RESCEU observational cohort study followed 1040 relatively healthy community-dwelling older adults aged 60 years and older during 2 consecutive winter seasons. Health care resource use and HRQoL were collected and analyzed during RSV episodes, and also during influenza episodes. Country-specific unit cost data were mainly obtained from national databases. Direct costs were estimated from a patient, health care provider, and health care payers’ perspective, whereas indirect costs were estimated from a societal perspective. Due to small sample size, no formal statistical comparisons were made. Results Thirty-six RSV and 60 influenza episodes were reported, including 1 hospitalization. Means (median; first-third quartile) of €26.4 (€5.5; 0–47.3) direct and €4.4 (€0; 0–0) indirect costs were reported per nonhospitalized RSV episode, and €42.5 (€36; 3.3–66.7) direct and €32.1 (€0; 0–0) indirect costs per nonhospitalized influenza episode. For RSV episodes, the utility value decreased from 0.896 (0.928; 0.854–0.953) to 0.801 (0.854; 0.712–0.937) from preseason to 1 week after symptom onset; for influenza, the change was from 0.872 (0.895; 0.828–0.953) to 0.664 (0.686; 0.574–0.797). Conclusions The average costs and HRQoL estimates of older adults treated outside the hospital can be used to inform the design of future studies and the decision making regarding interventions to prevent RSV infection in older adults. Larger studies are needed to provide better country-specific and complementary cost estimates and to allow for formal statistical comparison of costs between RSV and influenza. Clinical Trials Registration NCT03621930.

Emergency room admissions have decreased globally during the COVID-19 pandemic, particularly for respiratory diseases. We evaluated hospital admissions for respiratory diseases in the first year of the Italian pandemic and compared them with the corresponding period in 2016-2017.The study was carried out at the Sapienza University in Rome, Italy, and covered 9 March to 28 February 2020-2021 and 2016-2017. We tested 85 hospitalised children who were negative for the virus that causes COVID-19 in 2020-2021 and compared them with 476 hospitalised children from 2016-2017, as we had also tested nasal washing samples for 14 respiratory viruses during that period.Hospitalisations for acute respiratory tract infections were 82.2% lower in 2020-2021 than 2016-2017. The respiratory syncytial virus (RSV) and several other viruses were detected less frequently during the pandemic. An extraordinary finding was that rhinoviruses remained seasonal. In 2020-2021, we detected a virus in 54.1% of the hospitalised children: rhinoviruses in 41, RSV in 4 and other viruses in 1. This was significantly lower than the 71.6% in 2016-2017: RSV in 130, rhinoviruses in 128 and other viruses in 83.Pandemic measures dramatically reduced childhood respiratory infections, particularly RSV, but were less effective at reducing rhinoviruses.

Background Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs. Methods Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease. Results We estimate an annual average of 13 517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40 000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb. Conclusions Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential.

Acute respiratory infections (ARIs) are one of the leading causes of illness and death among community members worldwide. Viral infections are the most common agents estimated to be involved in these patients. This study aimed to investigate the prevalence of human respiratory syncytial virus (hRSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among children with ARIs. This study evaluated the presence of SARS-CoV-2 and hRSV in 168 throat and nasopharyngeal swab samples using real-time RT-PCR. All samples were collected from children under 5 years old with ARIs who attended Children's Medical Center, Tehran, Iran, and sent to the Iranian National Influenza Center with appropriate conditions in 2021. Chi-square and Fisher's exact tests were used for comparison of the data of the prevalence of hRSV and SARS-CoV-2 infections among children. Of 168 patients examined, 95 (57%) were male and 73 (43%) female. Out of them, 47 (28%) cases were younger than 1 year old and 121 cases (72%) were 1-5 years old. The most common clinical manifestations of patients were cough (78%), nausea (31%), diarrhea (27%), and fever (18%). Among 168 patients, no hRSV was detected, while the SARS-CoV-2 genome was identified in 16 (9.5%) patients. Among 16 positive cases of SARS-CoV-2, 8 (50%) were under 1 year old and 8 positive cases were 1-5 years old. This study was performed at cold months of the year but due to the coronavirus disease 2019 pandemic and adherence to health protocols, school closures, and virtual classes, no cases of hRSV infections were identified.

Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease in the pediatric population. An unexpected sudden upsurge of RSV infections among children was observed in September 2021 in Greece. Forty-one rhinopharyngeal samples from children under the age of 2 years with confirmed RSV bronchiolitis were tested to identify the genotype(s) of the RSV strain(s). The children were hospitalized during September-November 2021 in three tertiary hospitals in northern Greece. A one-step RT-PCR which amplifies a fragment of the second hypervariable region of the G protein gene was applied. PCR products were sequenced, and phylogenetic analysis was performed. Most (80.5%) RSV cases were typed as RSV-A, with RSV-B accounting for 19.5% of cases. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. As the same genotypes were detected in cases observed during 2016-2018 in northern Greece, it was suggested that the early upsurge of infections was not related to the emergence of novel strain(s), but it was the result of the absence of immunity among children and their mothers due to the restriction measures taken during the COVID-19 pandemic in the previous RSV season. Awareness is needed to diagnose even the out-of-season RSV infections, while molecular epidemiology plays a key role in monitoring the efficacy of currently available therapeutics and for those under development.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. METHODS: We randomly assigned, in a 2:1 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection. RESULTS: A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P

Respiratory syncytial virus (RSV) is an RNA virus spread via droplets. Children are predominately affected, with a significant burden in the under 1s. The burden of disease across both children and adults and management is rarely reported. We completed a retrospective study looking at the characteristics of all patients admitted with a positive RSV PCR throat swab were reviewed from a large tertiary hospital in the United Kingdom over the 2019/2020 season. Four hundred six paediatric patients and 81 adult patients were included. Ninety-four percent (76/81) of adult patients had comorbidities compared with 20% (81/406) of children. In adults Chest radiograph was normal in 46% (37/81). Thirty-six percent (29/81) showed consolidation. Viral coinfection was common among children 158 (39%). Forty (10%) of children were admitted to pediatric intensive care and 7 (9%) of adults were admitted to intensive care unit. No children and 6 (7%) of adults admitted with RSV died. RSV is associated with a significant morbidity. Mortality in adults admitted to Intensive Care Unit was high. Coinfection with other viruses is common in children. The use of antibiotics was higher than expected, although C-reactive protein and Chest radiograph suggested secondary bacterial infection is more common in adults.

We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008-9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of 1 transplant, age ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7-12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.