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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 -
BMJ Global Health Feb 2023Respiratory syncytial virus (RSV) is the principal cause of acute lower respiratory infections (ALRI) among infants worldwide, and an important cause of morbidity,...
Impact of breastfeeding on the incidence and severity of respiratory syncytial virus (RSV)-associated acute lower respiratory infections in infants: a systematic review highlighting the global relevance of primary prevention.
BACKGROUND
Respiratory syncytial virus (RSV) is the principal cause of acute lower respiratory infections (ALRI) among infants worldwide, and an important cause of morbidity, hospitalisation and mortality. While infants are universally exposed to RSV, most mortality occurs among normal term infants from low-income and middle-income countries. Breastfeeding has been suggested to have a protective effect against RSV infection. This study aims to determine the association of breastfeeding on the frequency and severity of RSV-associated ALRI among infants.
METHODS
A systematic review was conducted using keywords and Medical Subject Headings on MEDLINE, PubMed, Google Scholar, EMBASE, MedRxiv and Cochrane Central Register of Controlled Trials. Full-text articles published in English from 2000 to 2021 that studied exclusively or partially breastfed infants who developed RSV-associated ALRI <12 months of age were included. Covidence software-based evidence extraction and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines were followed. Quality of evidence was analysed using UK National Service Framework grading and the risk-of-bias assessment using Robvis.
RESULTS
Among 1368 studies screened, 217 qualified full-text review and 198 were excluded based on pre-agreed criteria. Nineteen articles published from 12 countries that included 16 787 infants from 31 countries (of which 8 middle-income) were retained for analysis. Results indicate that non-breastfeeding practices pose a significant risk for severe RSV-associated ALRI and hospitalisation. Exclusive breastfeeding for >4-6 months significantly lowered hospitalisation, length of stay, supplemental oxygen demand and admission to intensive care units.
CONCLUSION
In the context of no effective or standardised treatment for established RSV-associated ALRI, available evidence suggest that breastfeeding is associated with lower frequency and severity of RSV-associated ALRI, based on observational studies of variable grades of evidence and risk-of-bias. With both exclusive and partial breastfeeding benefiting infants who develop RSV-associated ALRI, breastfeeding should be promoted globally as an adjunct primary prevention; in addition to emerging immunoprophylaxis and maternal immunisation strategies.
Topics: Female; Infant; Humans; Respiratory Syncytial Viruses; Breast Feeding; Incidence; Respiratory Tract Infections; Primary Prevention
PubMed: 36746518
DOI: 10.1136/bmjgh-2022-009693 -
The Journal of Infectious Diseases Jul 2023Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection.
METHODS
EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types.
RESULTS
Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable.
CONCLUSIONS
RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.
Topics: Adult; Humans; Respiratory Syncytial Virus Infections; Sensitivity and Specificity; Respiratory Syncytial Virus, Human; Nasopharynx; Diagnostic Techniques and Procedures; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 36661222
DOI: 10.1093/infdis/jiad012 -
Journal of Global Health Jan 2023Globally, the respiratory syncytial virus (RSV) is the most common etiologic agent of acute respiratory illnesses in children. However, its burden has not been well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, the respiratory syncytial virus (RSV) is the most common etiologic agent of acute respiratory illnesses in children. However, its burden has not been well addressed in developing countries. We aimed to estimate the molecular epidemiology of RSV in children less than 18 years of age with acute respiratory infections in Africa by conducting a systematic review and meta-analysis.
METHODS
We systematically searched PubMed, Scopus, CINAHL, and Global Index Medicus databases to identify studies published from January 1, 2002, to April 27, 2022, following the PRISMA 2020 guideline. We assessed the study quality using the Joanna Brigg's Institute (JBI) critical appraisal checklists. We conducted a qualitative synthesis by describing the characteristics of included studies and performed the quantitative synthesis with random effects model using STATA-14. We checked for heterogeneity with Q statistics, quantified by I, and determined the prediction interval. We performed subgroup analyses to explain the sources of heterogeneity and assessed publication biases by funnel plots augmented with Egger's test.
RESULTS
Eighty-eight studies with 105 139 participants were included in the review. The overall pooled prevalence of RSV in children <18 years of age was 23% (95% confidence interval (CI) = 20, 25%). Considerable heterogeneity was present across the included studies. The adjusted prediction interval was found to be 19%-27%. Heterogeneities were explained by subgroups analyses. The highest prevalence of RSV was found among inpatients, 28% (95% CI = 25, 31%) compared with inpatients/outpatients and outpatients, with statistically significant differences (P < 0.01). The RSV estimate was also highest among those with acute lower respiratory tract illnesses (ALRTIs), 28% (95% CI = 25, 31%) compared with acute upper respiratory tract illnesses (AURTIs) and both acute upper/lower respiratory manifestations, with statistically different prevalence (P < 0.01). RSV infection estimates in each sub-region of Africa were statistically different (P < 0.01). There were no statistically significant differences in RSV infections by designs, specimen types, and specimen conditions, despite them contributing to heterogeneity.
CONCLUSIONS
We found a high prevalence of RSV in pediatric populations with acute respiratory tract illnesses in Africa, highlighting that the prevention and control of RSV infections in children deserve more attention.
REGISTRATION
PROSPERO CRD42022327054.
Topics: Child; Humans; Infant; Molecular Epidemiology; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Africa; Respiratory Tract Infections
PubMed: 36637855
DOI: 10.7189/jogh.13.04001 -
European Respiratory Review : An... Dec 2022Respiratory syncytial virus (RSV) significantly impacts the health of older and high-risk adults (those with comorbidities). We aimed to synthesise the evidence on RSV... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory syncytial virus (RSV) significantly impacts the health of older and high-risk adults (those with comorbidities). We aimed to synthesise the evidence on RSV disease burden and RSV-related healthcare utilisation in both populations.
METHODS
We searched Embase and MEDLINE for papers published between 2000 and 2019 reporting the burden and clinical presentation of symptomatic RSV infection and the associated healthcare utilisation in developed countries in adults aged ≥60 years or at high risk. We calculated pooled estimates using random-effects inverse variance-weighted meta-analysis.
RESULTS
103 out of 3429 articles met the inclusion criteria. Among older adults, RSV caused 4.66% (95% CI 3.34-6.48%) of symptomatic respiratory infections in annual studies and 7.80% (95% CI 5.77-10.45%) in seasonal studies; RSV-related case fatality proportion (CFP) was 8.18% (95% CI 5.54-11.94%). Among high-risk adults, RSV caused 7.03% (95% CI 5.18-9.48%) of symptomatic respiratory infections in annual studies, and 7.69% (95% CI 6.23-9.46%) in seasonal studies; CFP was 9.88% (95% CI 6.66-14.43%). Data paucity impaired the calculation of estimates on population incidence, clinical presentation, severe outcomes and healthcare-related utilisation.
CONCLUSIONS
Older and high-risk adults frequently experience symptomatic RSV infection, with appreciable mortality; however, detailed data are lacking. Increased surveillance and research are needed to quantify population-based disease burden and facilitate RSV treatments and vaccine development.
Topics: Humans; Aged; Respiratory Syncytial Virus Infections; Developed Countries; Hospitalization; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 36384703
DOI: 10.1183/16000617.0105-2022 -
European Journal of Pediatrics Jan 2023Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and...
UNLABELLED
Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and life-threatening infections most commonly occur in the first years of life. In adults, elderly and immunocompromised people are most vulnerable. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics which are expected to become available in Europe within the next 2-10 years. Understanding the true burden of childhood RSV disease will become very important to support public health authorities and policy makers in the assessment of new therapeutic opportunities against RSV disease. A systematic literature search was performed to map local data on the burden of RSV disease and to evaluate available RSV surveillance systems. A group of 9 paediatric infectious diseases specialists participated in an expert panel. The purpose of this meeting was to evaluate and map the burden associated with RSV infection in children, including patient pathways and the epidemiological patterns of virus circulation in Belgium. Sources of information on the burden of RSV disease in Belgium are very limited. For the outpatient setting, it is estimated that 5-10% of young patients seen in primary care are referred to the hospital. Around 3500 children between 0 and 12 months of age are hospitalized for RSV-bronchiolitis every year and represent the majority of all hospitalizations. The current Belgian RSV surveillance system was evaluated and found to be insufficient. Knowledge gaps are highlighted and future perspectives and priorities offered.
CONCLUSION
The Belgian population-based RSV surveillance should be improved, and a hospital-led reporting system should be put in place to enable the evaluation of the true burden of RSV disease in Belgium and to improve disease management in the future.
WHAT IS KNOWN
• RSV bronchiolitis is a very important cause of infant hospitalization. • The burden of disease in the community is poorly studied and underestimated.
WHAT IS NEW
• This expert opinion summarizes knowledge gaps and offers insights that allow improvement of local surveillance systems in order to establish a future-proof RSV surveillance system.
Topics: Humans; Infant; Infant, Newborn; Belgium; Bronchiolitis; Hospitalization; Population Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 36371521
DOI: 10.1007/s00431-022-04698-z -
Influenza and Other Respiratory Viruses Jan 2023Respiratory syncytial virus (RSV)-associated acute respiratory infection (ARI) is an underrecognized cause of illness in older adults. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory syncytial virus (RSV)-associated acute respiratory infection (ARI) is an underrecognized cause of illness in older adults. We conducted a systematic literature review and meta-analysis to estimate the RSV disease burden in adults ≥60 years in high-income countries.
METHODS
Data on RSV-ARI and hospitalization attack rates and in-hospital case fatality rates (hCFR) in adults ≥60 years from the United States, Canada, European countries, Japan, and South Korea were collected based on a systematic literature search (January 1, 2000-November 3, 2021) or via other methods (citation search, unpublished studies cited by a previous meta-analysis, gray literature, and an RSV-specific abstract booklet). A random effects meta-analysis was performed on estimates from the included studies.
RESULTS
Twenty-one studies were included in the meta-analysis. The pooled estimates were 1.62% (95% confidence interval [CI]: 0.84-3.08) for RSV-ARI attack rate, 0.15% (95% CI: 0.09-0.22) for hospitalization attack rate, and 7.13% (95% CI: 5.40-9.36) for hCFR. In 2019, this would translate into approximately 5.2 million cases, 470,000 hospitalizations, and 33,000 in-hospital deaths in ≥60-year-old adults in high-income countries.
CONCLUSIONS
RSV disease burden in adults aged ≥60 years in high-income countries is higher than previously estimated, highlighting the need for RSV prophylaxis in this age group.
Topics: Humans; Infant; Middle Aged; Aged; Developed Countries; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Hospitalization; Cost of Illness
PubMed: 36369772
DOI: 10.1111/irv.13031 -
BMC Infectious Diseases Oct 2022Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG... (Meta-Analysis)
Meta-Analysis
Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96-100%) and specificity 100% (95% CrI 98-100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89-100) and 98% (95% CrI 88-100) respectively; specificity 100% (95% CrI 99-100) and 100% (95% CrI 99-100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators' performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.Protocol Registration: Prospero CRD42021272062.
Topics: Humans; Influenza A virus; Influenza B virus; Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Sensitivity and Specificity
PubMed: 36229786
DOI: 10.1186/s12879-022-07766-9 -
Journal of Global Health Sep 2022With the easing of COVID-19 non-pharmaceutical interventions, the resurgence of both influenza and respiratory syncytial virus (RSV) was observed in several countries... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the easing of COVID-19 non-pharmaceutical interventions, the resurgence of both influenza and respiratory syncytial virus (RSV) was observed in several countries globally after remaining low in activity for over a year. However, whether co-infection with influenza or RSV influences disease severity in COVID-19 patients has not yet been determined clearly. We aimed to understand the impact of influenza/RSV co-infection on clinical disease severity among COVID-19 patients.
METHODS
We conducted a systematic literature review of publications comparing the clinical severity between the co-infection group (ie, influenza/RSV with SARS-CoV-2) and mono-infection group (ie, SARS-CoV-2), using the following four outcomes: need or use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation, and deaths. We summarized the results by clinical outcome and conducted random-effect meta-analyses where applicable.
RESULTS
Twelve studies reporting a total of 7862 COVID-19 patients were included in the review. Influenza and SARS-CoV-2 co-infection were found to be associated with a higher risk of ICU admission (five studies, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.64-2.68) and mechanical ventilation (five studies, OR = 2.31, 95% CI = 1.10-4.85). No significant association was found between influenza co-infection and need/use of supplemental oxygen or deaths among COVID-19 patients (four studies, OR = 1.04, 95% CI = 0.37-2.95; 11 studies, OR = 1.41, 95% CI = 0.65-3.08, respectively). For RSV co-infection, data were only sufficient to allow for analyses for the outcome of deaths, and no significant association was found between RSV co-infection and deaths among COVID-19 patients (three studies, OR = 5.27, 95% CI = 0.58-47.87).
CONCLUSIONS
Existing evidence suggests that co-infection with influenza might be associated with a 2-fold increase in the risk for ICU admission and for mechanical ventilation among COVID-19 patients whereas evidence is limited on the role of RSV co-infection. Co-infection with influenza does not increase the risk of death in COVID-19 patients.
REGISTRATION
PROSEPRO CRD42021283045.
Topics: COVID-19; Coinfection; Humans; Influenza, Human; Oxygen; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; SARS-CoV-2
PubMed: 36112521
DOI: 10.7189/jogh.12.05040 -
The Journal of Infectious Diseases Aug 2022The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.
BACKGROUND
The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.
METHODS
We systematically reviewed studies of RSV and bronchiolitis published 2000-2021 (data years, 1979-2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools.
RESULTS
We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6-11 months in 2006 to 50.1 per 1000 per year among infants aged 0-2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0-22.7 per 1000 in 1997-1999 and 1997-2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non-high-risk infants in 1997-2012.
CONCLUSIONS
Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.
Topics: Bronchiolitis; Humans; Infant; Infant, Newborn; Infant, Premature; Palivizumab; Patient Acceptance of Health Care; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United States
PubMed: 35968876
DOI: 10.1093/infdis/jiac201