Respiratory Syncytial Virus Prophylaxis Research Articles

1943. RSV Prophylaxis for 29-34 Gestational Preemies. Are Current Guidelines Justified? Lessons from an Israeli Multicenter Off-seasonal Study

Abstract Background Respiratory syncytial virus (RSV) prophylaxis provided during the winter to infants born at 29–34-week gestational age (wGA) is controversial. We utilized the unprecedented opportunity of high load off-season RSV admissions with no prophylaxis given during the summer of 2021, to assess the impact of withholding palivizumab on the relative burden of hospitalized 29-34 wGA infants. Methods This was a national multi-center observational retrospective study in 11 medical centers in Israel. We included infants under 1 year-old, who were hospitalized with RSV between November 2017 and August 2021. Demographics and clinical data were extracted from the medical records. We categorized our cohort into a seasonal admissions group (November- March) when palivizumab was indicated, and an off-season admissions group (April-October) when palivizumab was not indicated. The primary outcome was the proportion of 29-34 wGA hospitalizations in each group. Secondary outcomes included clinical severity parameters. Results We included 4,340 children in our study; 57% were males, 61% were Jewish, and the median age at admission was 2.9 months (IQR 1.4-6.4). A total of 3,296 infants were admitted during the RSV season, and 1,044 were admitted off-season. The proportion of 29-34 wGA preemies was significantly higher in the off-season admissions group compared to the in season patients (7% vs 2.1%, p< 0.001). We found a significantly higher prevalence of Jewish (77% vs 57%, p=0.001) and higher socioeconomic status (55% vs 45%, p< 0.001) children in the group admitted off-season compared to those in season. Logistic regression analysis revealed that the relative-odds of 29-34 wGA preemies to be hospitalized off-season was 2.67 (95% CI: 1.8-3.9, p< 0.001) fold higher than in season, independent of ethnicity, socioeconomic-status, gender, age, or institution. Clinical severity parameters did not differ significantly between the groups. Flow chart of study participants The proportion of 29-34 wGA preterm infants out of total admissions categorized into seasonal and out of season RSV infections Clinical severity in the subgroup of 29-34 wGA preterm infants Conclusion Our results reveal a significant higher proportion of 29-34 wGA preemies among the children hospitalized during off-season periods, when RSV immunoprophylaxis was not indicated. These findings may support the current broad Israeli policy of administration. Disclosures All Authors: No reported disclosures

Respiratory Syncytial Virus Prophylaxis With Palivizumab Is Not Associated With Improved Lung Function in Infants of Very Low Birth Weight at Early School Age

BackgroundPrematurity and infection with respiratory syncytial virus (RSV) are major risk factors for impaired lung function beyond the neonatal period. Research QuestionTo examine the long-term effects of palivizumab immunoprophylaxis in the first year of life on lung function and frequency of bronchitis episodes in 5 to 6-year-old preterm infants. Study Design and MethodsPreterm infants with a birth weight below 1500 grams (Very low birth weight infants, VLBWI) were enrolled in a German Neonatal Network (GNN) cohort study between 2009 and 2016. Children were examined by a single follow-up team at 5 to 6 years of age. VLBWI who received at least five doses of palivizumab were compared with children who never received palivizumab. Analyses were stratified by bronchopulmonary dysplasia (BPD) and gestational age. We analysed forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, and the risk for respiratory tract infections at the age of 5 to 6 years via univariate analyses and linear and logistic regression models. ResultsOut of N = 1986 VLBWI with follow-up at 5-6 years, N = 951 (48%) received immunoprophylaxis with palivizumab. Children with BPD (N = 1019) had a much lower FEV1 than children without BPD (median FEV1 z-score -1.51 vs. -1.09; p< 0.001). However, FEV1 in children with BPD was not altered by palivizumab (median FEV1 z-score in 698 children with BPD and palivizumab: -1.57; IQR -0.75 to -2.43 vs. 320 children with BPD without palivizumab: -1.37; IQR -0.69 to -2.25; p= 0.1). As for FEV1, we did not find any protective effects of palivizumab for other endpoints or in other risk groups. InterpretationPalivizumab immunoprophylaxis in VLBWI is not associated with improved lung function or lower rates of respiratory tract infections in early school-age infants.

Summer 2023 ACIP Update: RSV Prevention and Updated Recommendations on Other Vaccines.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention (CDC), normally meets three times per year to develop US vaccine recommendations. The ACIP met June 21-23, 2023, to discuss respiratory syncytial virus (RSV) vaccines, influenza vaccines, pneumococcal vaccines, meningococcal vaccines, and COVID-19 vaccines. The ACIP also held a special meeting on August 3, 2023 to discuss RSV prophylaxis in infants. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include a new recommendation for the monoclonal antibody nirsevimab for prevention of RSV disease in all infants, recommendations regarding use of 20-valent pneumococcal conjugate vaccine (PCV20), and discussion of potential forthcoming changes to meningococcal and COVID-19 vaccination recommendations.

Seasonal Prevalence of Respiratory Pathogens Among Children in the United Arab Emirates: A Multicenter Cross-Sectional Study in the Pre-COVID-19 Era.

Background Viral respiratory infections in children pose a significant burden on healthcare facilities globally. In the United Arab Emirates (UAE) these account for 15% of all healthcare encounters among children. However, the seasonal prevalence and molecular epidemiology of respiratory viral infections in the UAE remains unknown. We sought to determine trends in seasonal viral prevalence in order to monitor disease activity and optimize the timing of Respiratory Syncytial Virus (RSV) prophylaxis among high-risk infants in the UAE. Methods This cross-sectional multicenter study included children 0-18 years of age who presented to a large private healthcare group in Dubai, UAE, and had upper respiratory samples collected for multiplex polymerase chain reaction (mPCR) testing between January 1st and December 31st, 2019. Sociodemographic, clinical, and molecular data were examined for children who tested positive for any pathogen on the mPCR panel. Results A total of three thousand and ninety-eight infants and children had mPCR assays performed during the study period, of which 2427 (78.3%) were positive for any respiratory pathogen. The median age of our sample population was 39 months and 56.8% were male. Emergency room was the most common site (34.7%) of sample collection and the vast majority of children presented with fever (85.3%). Rhinovirus/enterovirus was the most prevalent viral infection (45%) throughout the year and peaked in September, followed by Influenza (20.2%), and RSV (17.1%). RSV season, defined as an infection prevalence of >10%, occurred from August to December with a peak in October. Adenovirus (15.6%) infections peaked in June and accounted for 43% of hospitalizations in our study (p<0.05). Viral co-infections with RSV and rhinovirus/enterovirus were most common and observed in 19.9 % of children. Conclusion Rhinovirus/enterovirus is the most prevalent viral pathogen throughout the calendar year among the pediatric population in the UAE. RSV season begins earlier than reported in other countries regionally, hence RSV prophylaxis should be initiated in August to optimize protection among high-risk infants.

Cost-effectiveness of nirsevimab and palivizumab for respiratory syncytial virus prophylaxis in preterm infants 29–34 6/7 weeks' gestation in the United States

Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population. A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty. Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective. Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical.

Cost-Effectiveness of an RSVpreF Vaccine for Prevention of Respiratory Syncytial Virus Outcomes in Infants

&#x0D; From CADTH’s search of the economic literature, 4 economic studies were identified that assessed the cost-effectiveness of respiratory syncytial virus (RSV) immunization during pregnancy in high-income countries, including 1 study set in Nunavik, Quebec. Only 1 of these studies specifically considered the product of interest (RSVpreF), and only in a scenario analysis.&#x0D; In the 4 identified studies that evaluated the cost-effectiveness of RSV immunization during pregnancy, the outcomes predicted by the models focused on those related to infants. There is a lack of evidence on outcomes — thus cost-effectiveness — for the persons who are pregnant.&#x0D; The results from the 4 studies varied considerably. RSV immunization during pregnancy ranged from being more effective and associated with lower total costs (dominant) to more than $200,000 per quality-adjusted life-year gained when compared with no intervention. The results depended on the modelled region, efficacy, pricing, and severity of the RSV season.&#x0D; In 2 studies, year-round RSV immunization during pregnancy was not considered cost-effective compared with seasonal RSV prophylaxis with long-acting monoclonal antibodies (mAbs), such as nirsevimab, when the price per dose was the same as that of the long-acting mAb. RSV immunization during pregnancy was estimated to become cost-effective when its acquisition cost per dose was 2 to 5 times lower than that of the long-acting mAb.&#x0D;

Exploring the adoption of less restricted criteria for respiratory syncytial virus prophylaxis in late preterm infants: insights from a retrospective analysis

BackgroundPreterm infants born between 33 and 35 weeks of gestational age (wGA) have been considered a “major underserved population” and ineligible to receive palivizumab (PLV), the only drug authorized to date for respiratory syncytial virus (RSV) prophylaxis, by current international guidelines. In Italy, such a vulnerable population is currently eligible for prophylaxis, and, in our region, specific risk factors are taken into consideration (SINLazio score) to target prophylaxis for those at highest risk. Whether the adoption of less or more restrictive eligibility criteria for PLV prophylaxis would translate into differences in bronchiolitis and hospitalization incidence is not known.Materials and methodsA retrospective analysis was conducted in 296 moderate-to-late preterm infants (born between 33 and 35+6 weeks) who were being considered for prophylaxis in two epidemic seasons: 2018–2019 and 2019–2020. The study participants were categorized according to both the SINLazio score and the Blanken risk scoring tool (BRST), which was found to reliably predict RSV-associated hospitalization in preterm infants on the basis of three risk factor variables.ResultsBased on the SINLazio score, approximately 40% of infants (123/296) would meet the criteria to be eligible for PLV prophylaxis. In contrast, none of the analyzed infants would be considered eligible for RSV prophylaxis on the basis of the BRST. A total of 45 (15.2%) bronchiolitis diagnoses were recorded on average at 5 months of age in the overall population. Almost seven out of 10 (84/123) patients exhibiting ≥3 risk factors to be eligible for RSV prophylaxis according to SINLazio criteria would not be receiving PLV if they were categorized on the basis of the BRST. Bronchiolitis occurrence in patients with a SINLazio score ≥3 was approximately 2.2 times more likely than that in patients with a SINLazio score &amp;lt;3. PLV prophylaxis has been associated with a 91% lower risk of requiring a nasal cannula.ConclusionOur work further supports the need for targeting late preterm infants for RSV prophylaxis and calls for an appraisal of the current eligibility criteria for PLV treatment. Therefore, adopting less restrictive criteria may ensure a comprehensive prophylaxis of the eligible subjects, thus sparing them from avoidable short- and long-term consequences of RSV infection.

Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants

Background and objectiveTo assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32–35 weeks’ gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST).MethodsA decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included.ResultsCost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231).ConclusionsPalivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

Respiratory syncytial virus and its prophylaxis with palivizumab: exploring nurses' knowledge.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in children. Premature infants and infants with underlying health issues are at increased risk of developing severe RSV infection. Prophylactic treatment with palivizumab reduces their risk of hospitalisation. To measure nurses' knowledge of RSV and RSV prophylaxis and explore their perceived potential barriers to palivizumab administration to children in the acute hospital setting. A non-experimental, quantitative fixed study design was adopted. A 17-item online questionnaire was used to survey nurses caring for children under the age of 1 year in an acute children's teaching hospital. Questionnaires were completed by 144 nurses, giving a response rate of 53%. Respondents demonstrated an adequate knowledge of RSV and its prophylaxis but also some knowledge deficits, notably about the eligibility criteria for palivizumab. The most cited perceived potential barriers to palivizumab administration were uncertainty about which infants are eligible for it, forgetting to check whether a patient is due to receive a dose, parental refusal for treatment because their child is ill, and not knowing the contraindications of palivizumab. Front-line hospital staff have a crucial role in identifying infants eligible for prophylactic RSV treatment, in initiating prophylaxis in a timely manner, in avoiding missed or delayed palivizumab doses during infants' hospital stays, and in educating families about the importance of RSV prevention.

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein.

Respiratory syncytial virus (RSV) is a common cause of paediatric respiratory tract infection and causes a significant health burden in older adults. Natural immunity to RSV is incomplete, permitting recurrent symptomatic infection over an individual's lifespan. When combined with immunosenescence, this increases older adults' susceptibility to more severe disease symptoms. As RSV prophylaxis is currently limited to infants, older adults represent an important target population for RSV vaccine development. The relationship between RSV and our immune systems is complex, and these interactions require deeper understanding to tailor an effective vaccine candidate towards older adults. To date, vaccine candidates targeting RSV antigens, including pre-F, F, G (A), G (B), M2-1, and N, have shown efficacy against RSV infection in older adults in clinical trial settings. Although vaccine candidates have demonstrated robust neutralising IgG and cellular responses, it is important that research continues to investigate the RSV immune response in order to further understand how the choice of antigenic target site may impact vaccine effectiveness. In this article, we discuss the Phase 3 vaccine candidates being tested in older adults and review the hurdles that must be overcome to achieve effective protection against RSV.

Comparison of the Canadian vs. the international risk scoring tool for respiratory syncytial virus prophylaxis in moderate-to-late preterm infants.

The study objective was to compare the Pediatric Investigators Collaborative Network on Infections in Canada risk scoring tool (CRST) that determines need for respiratory syncytial virus (RSV) prophylaxis in infants 33-35 weeks gestational age during the RSV season, with the newly developed international risk scoring tool (IRST). Children 33-35 weeks gestational age born during the 2018-2021 RSV seasons were prospectively identified following birth and scored with the validated CRST and IRST, that comprises seven and three variables respectively, into low- moderate- and high-risk groups that predict RSV-related hospitalization. Correlations between total scores on the two tools, and cut-off scores for the low-, moderate- and high-risk categories were conducted using the Spearman rank correlation. Over a period of 3 RSV seasons, 556 infants were scored. Total risk scores on the CRST and the IRST were moderately correlated (rs = 0.64, p < 0.001). A significant relationship between the risk category rank on the CRST and the risk category rank on the IRST (rs = 0.53; p < 0.001) was found. The proportion of infants categorized as moderate risk for RSV hospitalization by the CRST and IRST were 19.6% (n = 109) and 28.1% (n = 156), respectively. The IRST may provide a time-efficient scoring alternative to the CRST with three vs. seven variables, and it selects a larger number of infants who are at moderate risk for RSV hospitalization for prophylaxis. A cost-utility analysis is necessary to justify country-specific use of the IRST, while in Canada a cost comparison is necessary between the IRST vs. the currently approved CRST prior to adoption.

Current methods of preventing infectious disease and managing febrile neutropenia in childhood cancer patients: a nationwide survey in Japan

Preventing infection and managing febrile neutropenia (FN) is mandatory for children with cancer undergoing chemotherapy. However, the current situation in Japan is unknown. We conducted a nationwide web-based questionnaire survey in 153 institutions treating childhood cancer in Japan. We asked about the type prophylaxis used to prevent infectious disease and manage FN. If patients with childhood cancer were managed by both pediatricians and surgeons at the same institution, we asked both to reply. We received replies from 117 departments at 111 centers: of these, 108 were from pediatricians. Laminar air flow for neutropenic patients, and frequent hand sanitization with ethanol, were widespread. Twenty-eight percent and forty percent of departments performed active surveillance by taking cultures from patients and the environment, respectively, before initiation of chemotherapy. Forty-four percent of departments administered prophylactic intravenous antibiotics according to patient status. Many departments measured serum (1,3)-β-D glucan, procalcitonin, and aspergillus galactomannan at the onset of FN. Twenty-eight percent of departments used carbapenem as empirical therapy for FN. Some departments used prophylactic granulocyte-colony stimulating factor for acute leukemia. Seventy-two percent of departments used prophylactic immunoglobulin for hypogammaglobinemia caused by chemotherapy. Palivizumab was administered widely for respiratory syncytial virus prophylaxis in immunocompromised infants. As a whole, intensive care for infectious prophylaxis or FN is applied in Japan; however, the methods vary among centers, and some are excessive or inadequate. Therefore, it is desirable to conduct clinical trials and establish adequate care protocols for infection in children with cancer in Japan.

Retinoic Acid-Inducible Gene I Activation Inhibits Human Respiratory Syncytial Virus Replication in Mammalian Cells and in Mouse and Ferret Models of Infection.

Infections caused by human respiratory syncytial virus (RSV) are associated with substantial rates of morbidity and mortality. Treatment options are limited, and there is urgent need for the development of efficient antivirals. Pattern recognition receptors such as the cytoplasmic helicase retinoic acid-inducible gene (RIG) I can be activated by viral nucleic acids, leading to activation of interferon-stimulated genes and generation of an "antiviral state." In the current study, we activated RIG-I with synthetic RNA agonists (3pRNA) to induce resistance to RSV infection in vitro and in vivo. In vitro, pretreatment of human, mouse, and ferret airway cell lines with RIG-I agonist before RSV exposure inhibited virus infection and replication. Moreover, a single intravenous injection of 3pRNA 1 day before RSV infection resulted in potent inhibition of virus replication in the lungs of mice and ferrets, but not in nasal tissues. These studies provide evidence that RIG-I agonists represent a promising antiviral drug for RSV prophylaxis.

Respiratory syncytial virus infections requiring hospitalization in patients with primary immunodeficiency

IntroductionThe aim of the study was to assess the incidence of hospital admission due to severe acute respiratory infection by respiratory syncytial virus (RSV-ARI) in children with primary immunodeficiencies (PIDs) and the severity of RSV-ARI in these patients. MethodsWe conducted a nationwide cross-sectional retrospective and prospective multicentre study in the 2011–2017 period. The study was performed in 15 Spanish hospitals and included children with PID who required hospital admission due to RSV-ARI. ResultsOut of 439 patients with PID followed up at participating hospitals, 13 (3%) required hospital admission due to RSV-ARI. The median age of admitted patients was 1.6 years (interquartile range, 0.5−2.2), and 7 were male. The types of PID most frequently associated with admission due to RSV-ARI were combined immunodeficiency (CID; 4/71; 6%) and CID with associated or syndromic features (CIDwASF; 6/147; 4%). Two of the 13 patients were receiving palivizumab for RSV prophylaxis, and 3 received potentially active therapies against RSV during the hospital stay. Viral coinfection was detected in 6 patients, 5 (39%) developed complications, and 4 (31%) required admission to the paediatric intensive care unit. There were no documented RSV-related deaths. ConclusionsIn the group of patients with PID, severe RSV infection requiring hospitalization is more frequent in patients with CID and CIDwASF, in whom special efforts should be made to prevent RSV infection. Further studies are needed to confirm these results.

Global Disease Burden of Respiratory Syncytial Virus in Preterm Children in 2019: A Systematic Review and Individual Participant Data Meta-Analysis Protocol.

Existing guidelines on respiratory syncytial virus (RSV) prophylaxis differ greatly by gestational age (GA) and other underlying risk factors, highlighting the data gaps in RSV disease burden among preterm infants. We will conduct a systematic review and individual participant data (IPD) meta-analysis of RSV global disease burden among preterm-born children. Three databases, Medline, Embase, and Global Health, will be searched for relevant studies on RSV disease burden for 2019 or before in preterm-born children published between 1 January 1995 and 31 December 2021. IPD will be sought by contacting the investigators identified from published literature and from existing collaboration networks. One-stage and 2-stage random-effects meta-analyses will be used to combine information from IPD and non-IPD studies to produce summary RSV burden estimates of incidence rate, hospital admission rate, and in-hospital case fatality ratio. The framework will be extended to examine subgroup(s) with the most substantial RSV disease burden.

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

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

Infecciones por virus respiratorio sincitial que requieren hospitalización en pacientes con inmunodeficiencias primarias

IntroductionThe aim of the study was to assess the incidence of hospital admission due to severe acute respiratory infection by respiratory syncytial virus (RSV-ARI) in children with primary immunodeficiencies (PIDs) and the severity of RSV-ARI in these patients. MethodsWe conducted a nationwide cross-sectional retrospective and prospective multicentre study in the 2011-2017 period. The study was performed in 15 Spanish hospitals and included children with PID who required hospital admission due to RSV-ARI. ResultsOut of 439 patients with PID followed up at participating hospitals, 13 (3%) required hospital admission due to RSV-ARI. The median age of admitted patients was 1.6years (interquartile range, 0.5-2.2), and 7 were male. The types of PID most frequently associated with admission due to RSV-ARI were combined immunodeficiency (CID; 4/71 [6%]) and CID with associated or syndromic features (CIDwASF; 6/147 [4%]). Two of the 13 patients were receiving palivizumab for RSV prophylaxis, and 3 received potentially active therapies against RSV during the hospital stay. Viral coinfection was detected in 6 patients, 5 (39%) developed complications, and 4 (31%) required admission to the paediatric intensive care unit. There were no documented RSV-related deaths. ConclusionsIn the group of patients with PID, severe RSV infection requiring hospitalization is more frequent in patients with CID and CIDwASF, in whom special efforts should be made to prevent RSV infection. Further studies are needed to confirm these results.

Changes in paediatric respiratory infections at a UK teaching hospital 2016–2021; impact of the SARS-CoV-2 pandemic

Objective To describe the impact of the SARS-CoV-2 pandemic on the incidence of paediatric viral respiratory tract infection in Oxfordshire, UK.Methods Data on paediatric Emergency Department (ED) attendances (0–15 years inclusive), respiratory virus testing, vital signs and mortality at Oxford University Hospitals were summarised using descriptive statistics.Results Between 1-March-2016 and 30-July-2021, 155,056 ED attendances occurred and 7,195 respiratory virus PCRs were performed. Detection of all pathogens was suppressed during the first national lockdown. Rhinovirus and adenovirus rates increased when schools reopened September-December 2020, then fell, before rising in March-May 2021. The usual winter RSV peak did not occur in 2020/21, with an inter-seasonal rise (32/1,000 attendances in 0–3 yr olds) in July 2021. Influenza remained suppressed throughout. A higher paediatric early warning score (PEWS) was seen for attendees with adenovirus during the pandemic compared to pre-pandemic (p = 0.04, Mann-Witney U test), no other differences in PEWS were seen.Conclusions SARS-CoV-2 caused major changes in the incidence of paediatric respiratory viral infection in Oxfordshire, with implications for clinical service demand, testing strategies, timing of palivizumab RSV prophylaxis, and highlighting the need to understand which public health interventions are most effective for preventing respiratory virus infections.

Respiratory syncytial virus bronchiolitis in congenital diaphragmatic hernia: A systematic review of prevalence rates and palivizumab prophylaxis.

The seasonality of respiratory syncytial virus (RSV) epidemics have been disrupted during the COVID-19 pandemic, possibly because of lockdowns and social restrictions reducing viral transmission. Given uncertainties around the severity of upcoming RSV bronchiolitis epidemics, debate exists whether palivizumab (RSV prophylaxis) should be administered to infants with Congenital Diaphragmatic Hernia (CDH), who may be vulnerable due to lung hypoplasia and pulmonary hypertension. To evaluate (1) if CDH infants have higher risk of admission with RSV bronchiolitis than infants in the general population; (2) if palivizumab prophylaxis may reduce this risk. We included all eligible studies examining the risk(s) of RSV-positive bronchiolitis requiring hospital admission in (1) CDH infants without palivizumab prophylaxis versus infants in the general population and (2) CDH infants with prophylaxis versus CDH infants without prophylaxis. The primary outcome evaluated was the risk of admission with RSV bronchiolitis. Data are reported descriptively and meta-analysed when appropriate. Three eligible retrospective cohort studies were identified: one study found CDH to be an independent risk factor for RSV hospitalisation (odds ratio, 3.30; 95% confidence interval [CI], 2.01-4.4); two studies compared RSV hospitalisation rates in CDH patients who had palivizumab versus those that did not. The pooled risk ratio was 1.11 (95% CI, 0.29-4.23; p = .88). Overall, the quality of evidence was considered poor and one study was industry funded. Whether CDH infants are at particular risk of severe bronchiolitis remains unclear. There is no evidence from this current systematic review that CDH infants should routinely receive palivizumab vaccination prophylaxis.