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JAMA Network Open Feb 2023Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.
OBJECTIVE
To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.
DATA SOURCES
In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.
STUDY SELECTION
Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework.
MAIN OUTCOMES AND MEASURES
The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use.
RESULTS
Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, -58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest.
CONCLUSIONS AND RELEVANCE
In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.
Topics: Male; Infant; Child; Humans; Antibodies, Monoclonal; Palivizumab; Respiratory Syncytial Viruses; Network Meta-Analysis; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Oxygen; Randomized Controlled Trials as Topic
PubMed: 36800182
DOI: 10.1001/jamanetworkopen.2023.0023 -
PloS One 2023Although respiratory syncytial virus (RSV) immunoprophylaxis is recommended for high-risk infants, the American Academy of Pediatrics (AAP) recommends against...
BACKGROUND
Although respiratory syncytial virus (RSV) immunoprophylaxis is recommended for high-risk infants, the American Academy of Pediatrics (AAP) recommends against immunoprophylaxis in the same season following a breakthrough hospitalization due to limited risk for a second hospitalization. Evidence in support of this recommendation is limited. We estimated population-based re-infection rates from 2011-2019 in children <5 years since RSV risk remains relatively high in this age group.
MATERIALS AND METHODS
Using claims data from private insurance enrollees, we established cohorts of children <5 years who were followed to ascertain annual (July 1-June 30) and seasonal (November 1- February 28/29) RSV recurrence estimates. Unique RSV episodes included inpatient encounters with RSV diagnosis ≥30 days apart, and outpatient encounters ≥30 days apart from each other as well as from inpatient encounters. The risk of annual and seasonal re-infection was calculated as the proportion of children with a subsequent RSV episode in the same RSV year/season.
RESULTS
Over the 8 assessed seasons/years (N = 6,705,979) and across all age groups annual inpatient and outpatient infection rates were 0.14% and 1.29%, respectively. Among children with a first infection, annual inpatient and outpatient re-infection rates were 0.25% (95% confidence interval (CI) = 0.22-0.28) and 3.44% (95% CI = 3.33-3.56), respectively. Both infection and re-infection rates declined with age.
CONCLUSION
While medically-attended re-infections contributed numerically only a fraction of the total RSV infections, re-infections among those with previous infection in the same season were of similar magnitude as the general infection risk, suggesting that a previous infection may not attenuate the risk for a re-infection.
Topics: Humans; Infant; Child; United States; Child, Preschool; Palivizumab; Reinfection; Antiviral Agents; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization
PubMed: 36795639
DOI: 10.1371/journal.pone.0281555 -
International Journal of Environmental... Jan 2023Respiratory syncytial virus (RSV) is the most common pathogen causing viral respiratory tract infections among younger children worldwide. The influence of...
Respiratory syncytial virus (RSV) is the most common pathogen causing viral respiratory tract infections among younger children worldwide. The influence of meteorological factors on RSV seasonal activity is well-established for temperate countries; however, in subtropical countries such as Malaysia, relatively stable temperate climates do not clearly support this trend, and the available data are contradictory. Better understanding of meteorological factors and seasonality of RSV will allow effective strategic health management relating to RSV infection, particularly immunoprophylaxis of high-risk infants with palivizumab. Retrospectively, from 2017 to 2021, we examined the association between various meteorological factors (rainfall, rainy days, temperature, and relative humidity) and the incidence of RSV in children aged less than 12 years in Kuala Lumpur, Malaysia. RSV activity peaked in two periods (July to August and October to December), which was significantly correlated with the lowest rainfall ( < 0.007) and number of rainy days ( < 0.005). RSV prevalence was also positively associated with temperature ( < 0.006) and inversely associated with relative humidity ( < 0.006). Based on our findings, we recommend that immunoprophylaxis with palivizumab be administered in children aged less than 2 years where transmission of RSV is postulated to be the highest after the end of two monsoon seasons.
Topics: Infant; Child; Humans; Child, Preschool; Retrospective Studies; Palivizumab; Malaysia; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Seasons; Meteorological Concepts
PubMed: 36767211
DOI: 10.3390/ijerph20031848 -
Infection and Drug Resistance 2023Respiratory syncytial virus (RSV) is one of the most common respiratory viruses. It not only affects young children but also the elderly and immunocompromised patients.... (Review)
Review
Respiratory syncytial virus (RSV) is one of the most common respiratory viruses. It not only affects young children but also the elderly and immunocompromised patients. After the emergence of SARS-CoV-2 and the corona virus disease 2019 (COVID-19) era, a dramatic reduction in RSV activity was found, which coincided with the implementation of public health and social measures (PHSMs). However, the correlation is more complicated than we initially thought. After PHSMs were gradually lifted, a seasonality shift and a delayed RSV outbreak with greater number of infected patients were found in numerous countries, such as Israel, Australia, South Africa, New Zealand, France, United States, and Japan. Several hypotheses and possible reasons explaining the interaction between SARS-CoV-2 and RSV were mentioned. Since RSV vaccinations are still under investigation, administration of palivizumab should be considered in high-risk patients. In the post-COVID-19 era, greater attention should be paid to a further resurgence of RSV. In this narrative review, we conducted a thorough review of the current knowledge on the epidemiology of RSV during the COVID-19 era, the out-of-season outbreak of RSV, and the data on co-infection with RSV and SARS-CoV-2.
PubMed: 36743336
DOI: 10.2147/IDR.S396434 -
Acta Medica Portuguesa May 2023An out-of-season increase in respiratory syncytial virus (RSV) incidence was observed in Portugal from June 2021 onwards, revealing a continuing surge in cases...
INTRODUCTION
An out-of-season increase in respiratory syncytial virus (RSV) incidence was observed in Portugal from June 2021 onwards, revealing a continuing surge in cases throughout 2021/2022 autumn/winter. We aimed to describe this out-of-season epidemic and define its epidemic period, by analysing RSV incidence from week 40 of 2020 (2020-W40) to week 18 of 2022 (2022-W18).
MATERIAL AND METHODS
Surveillance data on weekly RSV laboratory confirmed cases, in Portugal, was used to monitor RSV incidence using CUSUM test methodology for count data.
RESULTS
In 2021-W23, the CUSUM score identified a significant increase in the risk of RSV. By that time, the percentage of RSV positive tests rose from 1% in 2021-W22 (3/265) to 6% in 2021-W23 (18/298). Despite a sharp decrease in RSV incidence on 2021-W33 and on 2022-W02, the CUSUM score stayed over the limit up to 2022-W07, indicating that the RSV activity remained at an epidemic level. Distinct peaks of RSV cases were observed between 2021-W30 and 2021-W32 (average of 77 RSV cases per week) and between 2021-W39 and 2021-W41 (average of 79 RSV cases per week) with positivity rates around 60%.
CONCLUSION
An out-of-season RSV epidemic was identified, with a longer epidemic period compared with previous seasons. Possible reasons include relaxation of COVID-19 physical distancing measures and a greater proportion of population susceptible to disease. As several factors may change the pattern of RSV activity, countries should implement year-round surveillance RSV surveillance systems. These findings might have an impact on public health planning regarding future RSV surges, namely, on the palivizumab prophylaxis period for high-risk infants.
Topics: Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Epidemics; Portugal; Antibodies, Monoclonal, Humanized; Incidence; Humans; Male; Female; Infant, Newborn; Infant; Child, Preschool
PubMed: 36705636
DOI: 10.20344/amp.18589 -
Frontiers in Immunology 2022Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different...
PURPOSE
Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients.
METHODS
The genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated.
RESULTS
The highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1β in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1β in the first serum samples from patients with ON1 compared to those with BA9 of subtype B.
CONCLUSIONS
Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.
Topics: Child; Humans; Genotype; Interleukin-1alpha; Palivizumab; Phylogeny; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Immune Evasion
PubMed: 36703972
DOI: 10.3389/fimmu.2022.1084139 -
The Lancet. Child & Adolescent Health Mar 2023In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy... (Meta-Analysis)
Meta-Analysis
Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: a pooled analysis of randomised controlled trials.
BACKGROUND
In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy infants born preterm or at full term against medically attended RSV lower respiratory tract infection (LRTI). In the MEDLEY phase 2-3 trial in infants at higher risk for severe RSV infection, nirsevimab showed a similar safety profile to that of palivizumab. The aim of the current analysis was to assess the efficacy of nirsevimab using a weight-banded dosing regimen in infants born between 29 weeks gestational age and full term.
METHODS
Infants enrolled in the phase 2b and MELODY trials were randomised (2:1) to receive a single intramuscular injection of nirsevimab (infants weighing <5 kg received 50 mg; those weighing ≥5 kg received 100 mg) or placebo before the RSV season. Infants in MEDLEY were randomised (2:1) to receive one dose of nirsevimab (infants weighing <5 kg received 50 mg; those weighing ≥5 kg received 100 mg) followed by four monthly placebo doses, or five once-a-month intramuscular doses of palivizumab. We report a prespecified pooled efficacy analysis assessing the weight-banded dosing regimen proposed on the basis of the phase 2b and MELODY trials, in addition to extrapolated efficacy in infants with chronic lung disease, congenital heart disease, or extreme preterm birth (<29 weeks' gestational age) based on pharmacokinetic data from the phase 2-3 MEDLEY safety trial. For the pooled efficacy analysis, the primary endpoint was incidence of medically attended RSV LRTI through 150 days post-dose. The secondary efficacy endpoint was number of admissions to hospital for medically attended RSV LRTI. The incidence of very severe RSV LRTI was an exploratory endpoint, defined as cases of hospital admission for medically attended RSV LRTI that required supplemental oxygen or intravenous fluids. We also did a prespecified exploratory analysis of medically attended LRTI of any cause (in the investigator's judgement) and hospital admission for respiratory illness of any cause (defined as any upper respiratory tract infection or LRTI leading to hospital admission). Post hoc exploratory analyses of outpatient visits and antibiotic use were also done. Nirsevimab serum concentrations in MEDLEY were assessed using population pharmacokinetic methods and the pooled data from the phase 2b and MELODY trials. An exposure target was defined on the basis of an exposure-response analysis. To successfully demonstrate extrapolation, more than 80% of infants in MEDLEY had to achieve serum nirsevimab exposures at or above the predicted efficacious target.
FINDINGS
Overall, 2350 infants (1564 in the nirsevimab group and 786 in the placebo group) in the phase 2b and MELODY trials were included in the pooled analysis. Nirsevimab showed efficacy versus placebo with respect to the primary endpoint of medically attended RSV LRTI (19 [1%] nirsevimab recipients vs 51 [6%] placebo recipients; relative risk reduction [RRR] 79·5% [95% CI 65·9-87·7]). Consistent efficacy was shown for additional endpoints of RSV LRTI hospital admission (nine [1%] nirsevimab recipients vs 21 [3%] placebo recipients; 77·3% [50·3-89·7]) and very severe RSV (five [<1%] vs 18 [2%]; 86·0% [62·5-94·8]). Nirsevimab recipients had fewer hospital admissions for any-cause respiratory illness (RRR 43·8% [18·8-61·1]), any-cause medically attended LRTI (35·4% [21·5-46·9]), LRTI outpatient visits (41·9% [25·7-54·6]), and antibiotic prescriptions (23·6% [3·8-39·3]). Among infants with chronic lung disease, congenital heart disease, or extreme preterm birth in MEDLEY, nirsevimab serum exposures were similar to those found in the pooled data; exposures were above the target in more than 80% of the overall MEDLEY trial population (94%), including infants with chronic lung disease (94%) or congenital heart disease (80%) and those born extremely preterm (94%).
INTERPRETATION
A single dose of nirsevimab protected healthy infants born at term or preterm from medically attended RSV LRTI, associated hospital admission, and severe RSV. Pharmacokinetic data support efficacy extrapolation to infants with chronic lung disease, congenital heart disease, or extreme prematurity. Together, these data suggest that nirsevimab has the potential to change the landscape of infant RSV disease by reducing a major cause of infant morbidity and the consequent burden on caregivers, clinicians, and health-care providers.
FUNDING
AstraZeneca and Sanofi.
Topics: Female; Infant; Infant, Newborn; Humans; Palivizumab; Premature Birth; Antiviral Agents; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Heart Defects, Congenital; Lung Diseases; Randomized Controlled Trials as Topic
PubMed: 36634694
DOI: 10.1016/S2352-4642(22)00321-2 -
Italian Journal of Pediatrics Jan 2023In children with congenital heart disease (CHD) respiratory syncytial virus (RSV) infection may have a severe course, with increased risk of morbidity and mortality,... (Observational Study)
Observational Study
Prophylaxis protects infants with congenital heart disease from severe forms of RSV infection: an Italian observational retrospective study : Palivizumab prophylaxis in children with congenital heart disease.
BACKGROUND
In children with congenital heart disease (CHD) respiratory syncytial virus (RSV) infection may have a severe course, with increased risk of morbidity and mortality, requiring hospital admission and intensive care. The aim of the present study was to evaluate the effect of prophylaxis with palivizumab in preventing RSV-associated hospitalization in infants with CHD.
METHODS
We carried out an observational, retrospective study in a paediatric cardiology division at a secondary-care centre in Italy, extracting from the database children with CHD who, from November 2004 to March 2022, matched the criteria for palivizumab prophylaxis, to evaluate the hospitalization rate in CHD patients with and without palivizumab prophylaxis and their RSV-related hospitalization characteristics compared with a group of children without CHD and no other underlying clinical conditions (control group, CG), hospitalized for RSV infection.
RESULTS
One hundred twenty-eight children with CHD were enrolled in the study, mainly (71.9%) with increased pulmonary flow, and received palivizumab prophylaxis. Twenty-seven received hospital care for bronchiolitis. Almost all CHD patients hospitalized for bronchiolitis (26 out of 27) received partial prophylaxis (≤ 3 doses). CHD patients with bronchiolitis stay longer in the hospital than control (14.4 ± 21.7 days vs 6.2 ± 2.3 days) some of which require intensive care (n = 4).
CONCLUSIONS
Our study provides evidence of the efficacy of palivizumab in protecting patients with hemodynamically significant CHD under the age of 2 years from RSV disease and its life-threatening complications. Reducing hospitalisation rate, morbidity, and mortality in this category of patients, passive immune prophylaxis with palivizumab may impact healthcare resource availability and utilisation.
Topics: Infant; Humans; Child; Child, Preschool; Palivizumab; Retrospective Studies; Antiviral Agents; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus Infections; Heart Defects, Congenital; Hospitalization; Bronchiolitis
PubMed: 36631870
DOI: 10.1186/s13052-022-01399-z