Search Results (39)

In Cabo Verde, Acute Respiratory Infection caused by various pathogens was the most reported condition in children under 5 years old between 2014–2020, and the fourth leading cause of mortality in this age group, with Human Respiratory Syncytial Virus (HRSV) being one of the main etiological agents. However, limited literature on the subject hinders the study of its epidemiology and the evaluation of potential implications for public health. In this work, we developed and validated a primer collection for the amplification and sequencing of the G and F genes of HRSV, using a sequential workflow including conventional and semi-nested PCR, followed by Sanger sequencing. This strategy not only allowed for the identification of HRSV linages but also facilitated the detection of mutants in the HRSV F protein, a critical step towards evaluating and ensuring the continued efficacy of Nirsevimab or Palivizumab as prophylactic therapies. Our analysis revealed the presence of the HRSV lineages A.D.2.2.1, A.D.3, B.D.4.1.1, and B.D.E.1, corresponding to the globally circulating lineages during the study period (years 2019 and 2022). No previously described mutations in the F protein that confer resistance to Palivizumab and Nirsevimab were found. However, continuous monitoring of HRSV genotypes is crucial to promptly identifying resistant viruses, considering their potential impact on public health. Full article

Respiratory syncytial virus (RSV) continues as the major cause of acute lower respiratory tract infections in children around the world, and its substantial morbidity, particularly among infants and high-risk children, poses a significant burden on healthcare systems worldwide. RSV infections occur as a spectrum, ranging from mild upper respiratory symptoms to severe bronchiolitis and pneumonia, and the number of infections shows seasonal variations in different latitudes, as well as lasting impacts, reflecting the COVID-19 pandemic. The pathogenesis of the virus involves epithelial cell invasion and/or fusion to form syncytia, along with exaggerated immune-mediated responses. Disease severity is known to depend on viral load, strain variation, and host immune immaturity. Severe RSV infection during infancy is notably linked with long-term respiratory sequelae such as recurrent wheezing and asthma. Diagnosis is based on clinical suspicion and laboratory confirmation using rapid antigen testing or nucleic acid amplification tests, namely PCR. Non-pharmaceutical interventions, maternal vaccination, and prophylaxis with monoclonal antibodies, e.g., palivizumab and nirsevimab, a newly introduced long-acting agent, are efficient protective and preventive measures. Treatment is still, for the most part, supportive in nature and focuses on oxygen supplementation, hydration, and respiratory support for patients with more severe disease courses; however, the development of immunoprophylaxis and vaccine candidates shows promise for reducing the global burden of RSV. Full article

Background: In 2022, Romania started an RSV immunoprophylaxis program with Palivizumab for infants at high risk: preterm infants born before 35 weeks of pregnancy, infants born with congenital heart defects, and infants with chronic lung disease. We evaluated treatment adherence from August 2022 to March 2024. Method: We monitored the increase in the number of patients enrolled in the program and the number of collaborating neonatologists, family doctors, and pediatricians. Adherence to all doses of Palivizumab in enrolled patients was assessed by telephone interviews. The factors contributing to reduced adherence were identified. Results: Between August 2022 and March 2024, 1903 patients and 233 specialists were enrolled, a steady increase in both cohorts. The percentage of patients that complete their full sequence of doses decreases along with the number of doses (99% for one dose, 73% for two doses, 47% for three doses, 35% for four doses, and 22% for five doses) due to several factors. Conclusions: The program remains highly regarded by both physicians and caregivers, demonstrating its effectiveness as a valuable resource for educating parents and facilitating monoclonal antibody administration as a prevention method for RSV. Full article

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

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

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections, particularly affecting young infants, older adults, and individuals with comorbidities. Methods: This document, developed as a consensus by an international group of experts affiliated with the World Association of Infectious Diseases and Immunological Disorders (WAidid), focuses on recent advancements in RSV prevention, highlighting the introduction of monoclonal antibodies (mAbs) and vaccines. Results: Historically, RSV treatment options were limited to supportive care and the monoclonal antibody palivizumab, which required multiple doses. Recent innovations have led to the development of long-acting mAbs, such as nirsevimab, which provide season-long protection with a single dose. Nirsevimab has shown high efficacy in preventing severe RSV-related lower respiratory tract infections (LRTIs) in infants, reducing hospitalizations and ICU admissions. Additionally, new vaccines, such as RSVpreF and RSVpreF3, target older adults and have demonstrated significant efficacy in preventing LRTIs in clinical trials. Maternal vaccination strategies also show promise in providing passive immunity to newborns, protecting them during the most vulnerable early months of life. This document further discusses the global burden of RSV, its economic impact, and the challenges of implementing these preventative strategies in different healthcare settings. Conclusions: The evidence supports the integration of both passive (mAbs) and active (vaccines) immunization approaches as effective tools to mitigate the public health impact of RSV. The combined use of these interventions could substantially reduce RSV-related morbidity and mortality across various age groups and populations, emphasizing the importance of widespread immunization efforts. Full article

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization. Full article

Background: In-home palivizumab administration programs (PH) have shown promise in reducing RSV-associated infections. These programs may be particularly beneficial for children with medical complexity (CMC) by limiting their exposure to healthcare-associated infections (HAIs) from non-RSV-related pathogens during transportation and visits to medical facilities. Methods: In this prospective study, 41 children with CMC less than 2 years of age were randomized by their health insurance to receive PH or in the clinic (PC) during the RSV season (October 2018–April 2019). Patients were stratified by home ventilation. The primary outcome was the total number of face-to-face encounters. Secondary outcomes were unscheduled clinic visits and hospitalizations secondary to the non-RSV LRTIs. Standard frequentist and Bayesian analyses were performed. Results: All demographic factors and strata were matched between PH (“n” = 13, mean age 22 mo. SD ± 1), and PC (“n” = 28, mean age: 18 mo. SD ± 1). There was a decrease in the number of total face-to-face encounters (adjusted for mechanical ventilation and baseline diagnosis) [(4.5 vs. 8.8), (RR: 1.8, 95% CI: 1.3–2.5, p = 0.001)], and hospitalizations [(0.3 vs. 1.25), (RR: 3.8, 95% CI: 1.3–11.3, p = 0.016)], in the PH vs PC groups. Bayesian analysis showed a 93% probability of benefit in favor of fewer face-to-face encounters in the PH group. Conclusions: This study suggests that PH administration may reduce healthcare utilization in CMC. Minimizing exposure to healthcare facilities and supporting home-based interventions are promising strategies for this population. Full article

Background: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks’ gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). Methods: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. Results: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. Conclusions: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities. Full article

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs. Full article

Respiratory syncytial virus (RSV) is the most common cause of upper and lower respiratory tract infections in infants and young children. Virus-specific monoclonal antibodies (mAbs) can be used for diagnosis, prophylaxis, and research of RSV pathogenesis. A panel of 16 anti-RSV mAbs was obtained from mice immunized by RSV strain Long. Half of them had virus-neutralizing activity. According to Western blot all of these mAbs effectively bound native oligomeric (homodimeric and homotrimeric) forms of the RSV fusion (F) protein. Only five of the mAbs interacted with the monomeric form, and only one of these possessed neutralizing activity. None of these mAbs, nor the commercial humanized neutralizing mAb palivizumab, reacted with the denaturated F protein. Thus, interaction of all these mAbs with F protein had clear conformational dependence. Competitive ELISA and neutralization assays allowed the identification of nine antigenic target sites for the interaction of mAb with the F protein. Five partially overlapping sites may represent a complex spatial structure of one antigenic determinant, including one neutralizing and four non-neutralizing epitopes. Four sites (three neutralizing and one non-neutralizing) were found to be distinct. As a result of virus cultivation RSV–A, strain Long, in the presence of a large amount of one of the neutralizing mAbs, an escape mutant with a substitution, N240S, in the F protein, was obtained. Thus, it was shown for the first time that position 240 is critical for the protective effect of an anti-RSV antibody. To assess the ability of these mAbs to interact with modern RSV strains circulating in St. Petersburg (Russia) between 2014 and 2022, 73 RSV-A and 22 RSV-B isolates were analyzed. Six mAbs were directed to conserved epitopes of the F protein as they interacted most efficiently with both RSV subtypes in a fixed cell-ELISA and could be used for diagnostic assays detecting RSV. Full article

Respiratory Syncytial Virus (RSV) poses a severe threat to infants, particularly preterm infants. Palivizumab, the standard preventive prophylaxis, is primarily utilized in high-risk newborns due to its cost. This study assessed palivizumab’s effectiveness in preventing RSV infections in predominantly very preterm infants during their first year of life. Serum samples from a prospective multicentre cohort study in the Netherlands were analyzed to assess RSV infection rates by measuring IgG levels against three RSV proteins: nucleoprotein, pre-fusion, and post-fusion protein. Infants were stratified based on gestational age (GA), distinguishing very preterm (≤32 weeks GA) from moderate/late preterm (>32 to ≤36 weeks GA). In very preterm infants, palivizumab prophylaxis significantly reduced infection rates (18.9% vs. 48.3% in the prophylaxis vs. non-prophylaxis group. Accounting for GA, sex, birth season, and birth weight, the prophylaxis group showed significantly lower infection odds. In infants with >32 to ≤36 weeks GA, the non-prophylaxis group (55.4%) showed infection rates similar to the non-prophylaxis ≤32-week GA group, despite higher maternal antibody levels in the moderate/late preterm infants. In conclusion, palivizumab prophylaxis significantly reduces RSV infection rates in very premature infants. Future research should explore clinical implications and reasons for non-compliance, and compare palivizumab with emerging prophylactics like nirsevimab aiming to optimize RSV prophylaxis and improve preterm infant outcomes. Full article

Respiratory syncytial virus (RSV) is a well-known infant pathogen transmitted mainly by droplets. It is a leading cause of upper respiratory tract infections in children, usually with a mild course of illness. RSV has also been a threat to older people, especially those with underlying medical conditions. For a long time, prevention was limited to passive immunoprophylaxis with palivizumab for high-risk infants. There was a strong need to find other treatment or prevention methods against RSV infections. In addition, after the coronavirus disease 2019 (COVID-19) pandemic, some significant changes in RSV epidemiology have been observed. Researchers noticed the shift in RSV seasonality and age distribution and the increased number of cases in older infants and adults. All of these made the need to find other medical options even stronger. Fortunately, two protein-based vaccines against RSV have successfully passed all phases of clinical trials and have been approved for use by adults and older people. One of them is also approved for infants from birth to 6 months of age (after maternal immunisation during pregnancy) and for pregnant women between 24 and 36 weeks of pregnancy. Also, a new passive immunisation option named nirsevimab (a highly potent monoclonal antibody with a long half-life) is now available for the paediatric group. In this review, we will discuss the previous and current RSV prevention methods in the light of structural discoveries of RSV antigens. Full article

(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the “proof-of-principle” effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings. Full article

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections in the young, the elderly, and in immunodeficient patients. As such, the virus represents an important cause of morbidity and mortality worldwide. Development of monoclonal antibodies against RSV has resulted in a commercial prophylaxis, palivizumab (Synagis^®), and different antibodies that have improved our understanding of the structure of the viral proteins. In this study, a different immunization technique, subtractive immunization, was evaluated for its applicability to develop RSV-specific antibodies. One hybridoma which produced antibodies with the strongest staining of RSV infected cells, ATAC-0025, was selected for further characterization. This antibody belongs to the IgG1 class, has neutralizing capacity and recognizes the envelope F-protein. The antibody has a broad reactivity against a range of RSV reference strains and clinical isolates. Full article