Severe Respiratory Syncytial Virus Research Articles

Mouse Models of Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infection causes considerable mortality and morbidity in infants and young children. RSV infection appears to elicit a mixed immune response characterized by both Th1-type cells and Th2-type cells. This immune response, along with clinical features such as bronchiolitis, wheezing, and respiratory distress caused by RSV infection, presents similarly to many features of asthma and has led to an investigation into the link between severe RSV infection and asthma. RSV infection in mice is a powerful and useful tool for eliciting a Th2-type-driven immune response, lending mechanistic insight into severe RSV infection. Here we present several materials and methods used for propagating and purifying RSV, infecting mice with RSV, and analyzing samples from RSV-infected mice.

Review of respiratory syncytial virus infection among older adults and transplant recipients.

Respiratory syncytial virus (RSV) is a common cause of pulmonary infection among children and has been increasingly recognized as an important respiratory pathogen in older adults and immunocompromised hosts. Among older adults, RSV can lead to exacerbations of underlying lung and cardiac disease. It is also associated with significant morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients and may be associated with acute rejection and chronic lung allograft dysfunction among lung transplant recipients (LTRs). Current treatment options for severe RSV disease are limited, and there is a paucity of guidance on RSV treatment among older adults. This narrative review provides a comprehensive overview of RSV disease in older adults, HSCT recipients, and SOT recipients. Nosocomial spread has been reported, thus highlighting the importance of infection prevention and control measures to prevent outbreaks. Antivirals, monoclonal antibodies for immunoprophylaxis, and vaccine development are underway; however, future research is still needed in these critical areas.

Incidence and risk factors of hospitalisations for respiratory syncytial virus among children aged less than 2 years.

The study aim was to examine the incidence and risk factors of respiratory syncytial virus (RSV) bronchiolitis hospitalisations and disease severity among infants. We compared demographic and health characteristics of children aged 0-23 hospitalised for RSV bronchiolitis (cases, n = 1227) during 2008-2018 and control children (n = 554) of the same age admitted for non-respiratory disease. RSV antigen was detected in nasal swabs by immunochromatography. Multiple logistic regression models were applied. The average annual incidence of hospitalisation for RSV bronchiolitis was 12.6 per 1000 and 1.7 per 1000 (P < 0.001) among infants and toddlers, respectively, with winter seasonality (November-March). The risk of hospitalisation for RSV bronchiolitis increased among children aged 0-5 months (OR 7.66; 95% CI 5.61-10.45) and 6-11 months (OR 12.88, 95% CI 8.48-19.55), compared to those aged 12-23 months. Additional risk factors were living in low vs. higher socio-economic status towns (OR 1.49; 95% CI 1.14-1.95), having chronic medical conditions (OR 2.75; 95% CI 1.61-4.70), birth month (October-January vs. June-September) (OR 2.19; 95% CI 1.60-2.99) and history of stay in neonatal intensive care unit at birth (OR 2.37; 95% CI 1.27-4.41). Male children and those who had pneumonia were more likely to have severe RSV bronchiolitis. In conclusion, the burden of hospitalisations for RSV bronchiolitis is high, especially in young infants. Effective preventive measures such as RSV active vaccines can reduce the risk of hospitalisations for RSV bronchiolitis among these vulnerable groups.

Опыт проведения пассивной иммунизации против респираторно-синцитиальной вирусной инфекции — двенадцатый сезон

Respiratory syncytial virus (RSV) is the most common pathogenic agent responsible for respiratory viral infections in infants and young children. Therefore, the importance of research in the field has been driven by the need for effective preventive tools against RSV infection for children, especially those at high risk of severe RSV disease. Despite the on-going efforts to develop RSV vaccines, the passive immunization of children with a drug called palivizumab is the only reliable option for prophylactic use against RSV. The article presents data on the passive immunization carried out in Moscow in the 2021–2022 season, including the following: the patient routing, indications for immunization, and the organization of the immunization process. It also provides authors’ own data on the number of immunized preterm children born with low and extremely low birth weight which were collected during 11 immunization seasons. The article also reviews the structure of morbidity in this group of children. The authors emphasize a high prevalence of the comorbidity of respiratory and cardiovascular diseases. KEYWORDS: respiratory syncytial virus, preterm infants, very low body weight, very low birth weight (VLBW), extremely low birth weight (ELBW), bronchopulmonary dysplasia, immunoprophylaxis, palivizumab. FOR CITATION: Mironova A.K. The experience of passive immunization against respiratory syncytial viral infection: the twelfth season. Russian Medical Inquiry. 2022;6(11):659–666 (in Russ.). DOI: 10.32364/2587-6821-2022-6-11-659-666.

Factors Associated with Severe Lower Respiratory Tract Infection from Respiratory Syncytial Virus (RSV) in Thai Children

Objective: To determine the factors associated with severe ALRTI from RSV in children.Materials and Methods: A retrospective study of children aged 1-60 months were conducted from 2014 to 2018. Out of 269 patients diagnosed with RSV ALRTI, 100 children were enrolled in the study, 20 had severe RSV ALRTI, while 80 had non-severe RSV ALRTI as identified by the ReSVinet scale. A multivariable logistic model was conducted to select significant variables.Results: During the study period, 269 patients were diagnosed with RSV ALRTI. Mean age was 10.45 ± 3.53 months. Clinical manifestations of severe RSV ALRTI group had significant difference in abnormal general condition (P &lt; 0.001), tachypnea (P &lt; 0.001), SpO2 &lt; 85% (P &lt; 0.001), poor air entry in lungs (P &lt; 0.001), and retraction (P &lt; 0.001). The factors associated with severe RSV ALRTI group, were underlying congenital heart disease [aOR32.45; 95% CI 3.38-311.87, P = 0.003] and duration of hospital stay &gt;5 days [aOR 19.56; 95% CI 1.81-212.05, P = 0.014].Conclusion: Factors associated with severe RSV ALRTI in children were underlying congenital heart disease andduration of hospital stay &gt;5 days.

Effectiveness of palivizumab immunoprophylaxis in infants with respiratory syncytial virus disease in Colombia.

Respiratory syncytial virus (RSV) is one of the most important childhood infections. To evaluate the effectiveness and safety of palivizumab immunoprophylaxis in preterm infants at a high risk of severe respiratory syncytial virus infection during the RSV season in Colombia. A prospective observational non-comparative multicenter study in six Colombian cities. At the beginning of the RSV infection season, palivizumab prophylaxis, up to five doses, was administered to infants born at ≤32 weeks of gestation, infants younger than six months, infants under one year of age with bronchopulmonary dysplasia (BPD), infants one year or less of age with hemodynamically significant acyanotic and non-acyanotic congenital heart disease (CHD), and with follow-up during the immunoprophylaxis until one month after the last dose. The study enrolled 600 patients, 91.8% of which were born at ≤ 32 weeks of gestation. BPD was observed in 54.9% of infants. 49% were born at < 32 weeks gestation and presented BPD. 6.9% had hemodynamically significant acyanotic and non-acyanotic CHD 53.3% received three or more doses of palivizumab. The mean interval between doses was 39.6 days. 1.8% of patients were hospitalized due to a confirmed RSV infection. Overall mortality was 1.2%, whereas the mortality by RSV in infants undergoing prophylaxis was 0.2%. Palivizumab was a clinically effective, well-tolerated treatment in the Colombian population. The safety profile of palivizumab reflects the findings from previous studies in developed countries.

Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children.

Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population.Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children.Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children. To assess the effects of palivizumab for preventing severe RSV infection in children. We searched CENTRAL, MEDLINE, threeotherdatabases and two trialsregistersto 14 October 2021,together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021. We included randomised controlled trials (RCTs), including cluster-RCTs,comparing palivizumabgiven at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of agefrom both genders, regardless ofRSV infection history. DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results.Two review authors screened studies for selection, assessed risk of bias and extracted data.We used standard Cochrane methods.We used GRADE to assess the certainty of the evidence.The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay,RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days. We included five studies with a total of 3343 participants.All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumabevery month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low. Palivizumabreduceshospitalisation due to RSV infectionat two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64;5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortalityat two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15;5 studies, 3343 participants;moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39;3 studies, 2831 participants;moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reductionin hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97;5 studies, 3343participants; moderate certainty evidence). Palivizumabmay result in a large reductionin RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55;3 studies, 554participants;low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces thenumber of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44;1 study, 429 participants; high certainty evidence). The available evidence suggests that prophylaxis with palivizumabreduceshospitalisation due to RSV infection and results in little to no difference in mortality oradverse events. Moreover, palivizumabresults in a slight reductionin hospitalisation due to respiratory-related illness and may result in a large reductionin RSV infections. Palivizumabalso reduces thenumber of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumabon children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, childrenlacking breastfeeding, living inpoverty, or members of families in overcrowded situations.

Respiratory syncytial virus: promising progress against a leading cause of pneumonia

This World Pneumonia Day, as the global COVID-19 pandemic persists, another deadly and familiar, although under-recognised, respiratory virus requires attention: respiratory syncytial virus (RSV). RSV is responsible for acute respiratory illness, including pneumonia, in people of all ages. Globally, RSV is the most common cause of severe lower respiratory tract infection (LRTI) among infants younger than 6 months, almost all children are infected by age 2 years, and reinfection is common.1 Severe RSV can increase risk of bacterial coinfections and subsequent LRTI, particularly in young infants.

Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it with the host response to respiratory syncytial virus (RSV) and influenza virus. We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with influenza virus, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an IFN response in the nasal mucosa. The magnitude of the IFN response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2–infected adults had increased expression of genes involved in neutrophil activation and T-cell receptor signaling pathways compared with SARS-CoV-2–infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness.

The Changing Epidemiology of Respiratory Viruses in Children During the COVID-19 Pandemic: A Canary in a COVID Time.

The Changing Epidemiology of Respiratory Viruses in Children During the COVID-19 Pandemic: A Canary in a COVID Time.

Transplacental transfer of RSV antibody in Australian First Nations infants.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection hospitalisations in Aboriginal infants specifically those aged <6 months. Maternally derived RSV antibody (Ab) can protect against severe RSV disease in infancy. However, the efficiency of transplacental transfer of maternal anti-RSV Ab remains unknown in Aboriginal infants. We characterised RSV Ab in Australian First Nations mother-infant pairs (n = 78). We investigated impact of covariates including low birthweight, gestational age (GA), sex of the baby, maternal age and multiparity of the mother on cord to maternal anti-RSV Ab titre ratio (CMTR) using multivariable logistic regression model. All (n = 78) but one infant was born full term (median GA: 39 weeks, interquartile range: 38–40 weeks) and 56% were males. The mean log2 RSV Ab titre was 10.7 (SD ± 1.3) in maternal serum and 11.0 (SD ± 1.3) in cord serum at birth; a ratio of 1.02 (SD ±0.06). One-third of the pairs had a CMTR of <1 indicating impaired transfer. Almost 9% (7/78) of the term infants had cord RSV Ab levels below <log2 9. Covariates showed no effect on CMTR. Further mechanistic research is needed to determine the significance of these findings on RSV disease in First Nations children.

Maternal gut microbiome regulates immunity to RSV infection in offspring.

Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.

Severe bronchiolitis profiles and risk of asthma development in Finnish children

Recent studies support the existence of several entities under the clinical diagnosis of bronchiolitis. Among infants with severe bronchiolitis, distinct profiles have been differentially associated with development of recurrent wheezing by age 3 years. However, their associations with actual asthma remain unclear. Our aim was to study the association between severe bronchiolitis profiles identified by using a clustering approach and childhood asthma. Among 408 children (aged <2 years) hospitalized with bronchiolitis in Finland (in 2008-2010), latent class analysis identified 3 bronchiolitis profiles: profile A(47%), characterized by history of wheezing and/or eczema, wheezing during acute illness, and rhinovirus infection; profile BC (38%), characterized by severe illness and respiratory syncytial virus infection; and profile D (15%), characterized by the least severely ill children, including mostly children without wheezing and with rhinovirus infection. The children were followed by questionnaire 4 years later (86% [n= 348]) and through a nationwide social insurance database 7 years later (99% [n= 403]). Current asthma at the 4- and 7-year follow-ups was defined by regular use (according to parental report and medical records) or purchase (according to the social insurance database) of asthma control medication. Compared with risk of current asthma associated with profile BC, we observed increased risk of current asthma associated with profile Aboth at the 4-year follow-up (age- and sex-adjusted odds ratio= 2.42 [95% CI= 1.23-4.75]) and at the 7-year follow-up (age- and sex-adjusted odds ratio= 3.14 [95% CI= 1.33-7.42]). No significant difference in asthma risk was observed between profile D and profile BC. These longitudinal results provide further support for an association between a distinct severe bronchiolitis profile (characterized by a history of wheezing and/or eczema and rhinovirus infection) and risk of development childhood asthma.

Host inflammatory response is the major marker of severe respiratory syncytial virus infection in older adults

We aim to study the viral kinetics and host inflammatory response of RSV infection in older adults, and their correlation with disease severity. We performed a prospective observational study in adults with RSV infection. We serially collected nasal-throat swabs for quantification of RSV-A and RSV-B viral load, and peripheral blood samples for measurement of cytokine/chemokine concentrations. The study endpoints were (i) requiring supplemental oxygen therapy, and (ii) non-invasive ventilation, intensive care, or died within 30 days of admission. We performed multivariable logistic regression models to identify independent variables for severe disease. We enrolled 71 hospitalized patients and 10 outpatients treated for RSV infection (median age 75 years, 51% male, and 74% with comorbidities). Among hospitalized patients, 61% required supplemental oxygen therapy, and 18% had severe disease requiring non-invasive ventilation or intensive care, or died within 30 days. Inflammatory cytokine/chemokines IL-6, CXCL8/IL-8, CXCL9/MIG and CXCL10/IP-10 increased significantly during the acute phase of illness. IL-6 concentration was independently associated with severe disease after adjusting for confounding factors. RSV viral load was not associated with disease severity throughout the course of illness. Host inflammatory response is a major marker of severe disease in older adults with RSV infection.

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription.

SUMMARYHuman respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV.

Effectiveness and cost-effectiveness of RSV infant and maternal immunization programs: A case study of Nunavik, Canada.

BackgroundDespite passive immunization with palivizumab to select high-risk children under two years of age, the health and economic burden of respiratory syncytial virus (RSV) remains substantial. We evaluated the effectiveness and cost-effectiveness of immunization programs with new generations of RSV prophylactics, including long-acting monoclonal antibodies (LAMA) and maternal vaccines, in terms of reducing hospitalizations in Nunavik, a Canadian Arctic region.MethodsWe developed an agent-based model of RSV transmission and parameterized it with the demographics and burden of RSV in Nunavik, Québec. We compared various immunization strategies, taking into account the costs associated with program delivery and calculating the incremental cost-effectiveness ratio (ICER) using quality-adjusted life-years (QALYs) gained as a measure of effectiveness. Scenario analyses included immunization with palivizumab and LAMA for infants under one year of age, and maternal vaccination in mild, moderate, and severe RSV seasons. Data were analysed from November 1, 2019 to May 1, 2021.FindingsWe found that a Nunavik pilot program with palivizumab which included healthy full-term infants aged 0–2 months in addition to those considered high-risk for complicated RSV disease is not cost-effective, compared to offering palivizumab only to preterm/chronically ill infants under 1 year of age. Using LAMA as prophylaxis produces ICER values of CAD $39,414/QALY (95% Credible Interval [CrI]: $39,314–$40,017) in a mild season (moderately cost-effective) and CAD $5,255/QALY (95% CrI: $5,222–$5,307) in a moderate season (highly cost-effective). LAMA was a dominant (cost-saving with negative incremental costs and positive incremental effects) strategy in a severe RSV season. Maternal vaccination combined with immunization of preterm/chronically ill infants 3–11 months was also a dominant (cost-saving) strategy in all seasons.InterpretationThe switch from palivizumab in RSV immunization programs to new prophylactics would lead to significant savings, with LAMA being an effective strategy without compromising benefits in terms of reducing hospitalizations.

Evaluation of prognostic scores for respiratory syncytial virus infection in a French multicentre cohort of allogeneic haematopoietic stem cell transplantation recipients

Haematopoietic stem cell transplantation (HSCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. Two prognostic scores have been proposed to predict the risk of progression from upper respiratory tract infection (URTI) to lower respiratory tract infection (LRTI) and death. This was a multicentre study of allogeneic HSCT recipients diagnosed with an RSV infection between 2010 and 2019 who were retrospectively stratified by the immunodeficiency scoring index (ISI) and the severe immunodeficiency (SID) score. Endpoints were overall survival, RSV-attributable mortality and progression to LRTI after URTI. Prognostic analyses were performed using Cox regression models. We included 147 consecutive patients, including 94 (63.9%) initially diagnosed with URTI and 53 (36.1%) with LRTI. At 90 days, 14 patients had died (survival rate, 90.5%; 95% CI: 85.9–95.3), and nine deaths were attributable to RSV (attributable mortality rate, 5.4%; 95% CI: 2.5–10.0). The cumulative 90-day incidence of LRTI after URTI was 13.8% (95% CI: 7.8–21.6). Neither score showed prognostic value for mortality, while the ISI allowed the prediction of progression to LRTI (p = 0.0008). Our results do not fully replicate the results previously reported in cohorts of HSCT recipients. This may reflect the recent epidemiology of RSV infections in this HSCT cohort.

Nasopharyngeal Codetection of Haemophilus influenzae and Streptococcus pneumoniae Shapes Respiratory Syncytial Virus Disease Outcomes in Children.

The role of nasopharyngeal bacteria in respiratory syncytial virus (RSV) disease has been underestimated. We measured the frequency and burden of respiratory bacteria in the upper respiratory tract of infants with RSV infection over 7 respiratory seasons, and their impact on clinical outcomes. Children <2 years old with mild (outpatients, n=115) or severe (inpatients, n=566) RSV infection, and matched healthy controls (n=161) were enrolled. Nasopharyngeal samples were obtained for RSV, Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, and Haemophilus influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease. S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; P<.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (P<.01). In adjusted analyses, S. pneumoniae/H. influenzae codetection was independentlyassociated with greater odds of hospitalization, higher disease severity scores, need for supplemental oxygen, and longer hospitalization. Nasopharyngeal codetection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.

Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection

Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6-23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1-4.9) for the first 2 years, 2.3 (95% CI, 1.6-3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2-2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0-5 months. We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6-23 months compared to those whose first severe RSV infection occurred at 0-6 months. This provides new evidence for further assessment of the association and RSV intervention programs.

Factors associated with severe respiratory syncytial virus disease in hospitalised children: a retrospective analysis

BackgroundEarly recognition of children at risk of severe respiratory syncytial virus (RSV) lower respiratory tract infection is important as it informs management decisions. We aimed to evaluate factors associated with...