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The Journal of Infectious Diseases Aug 2022Respiratory syncytial virus (RSV) infections occur in human populations around the globe, causing disease of variable severity, disproportionately affecting infants and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory syncytial virus (RSV) infections occur in human populations around the globe, causing disease of variable severity, disproportionately affecting infants and older adults (>65 years of age). Immune responses can be protective but also contribute to disease. Experimental studies in animals enable detailed investigation of immune responses, provide insights into clinical questions, and accelerate the development of passive and active vaccination. We aimed to review the role of antibody and T-cell responses in relation to RSV disease severity in animals.
METHODS
Systematic review and meta-analysis of animal studies examining the association between T-cell responses/phenotype or antibody titers and severity of RSV disease. The PubMed, Zoological Record, and Embase databases were screened from January 1980 to May 2018 to identify animal studies of RSV infection that assessed serum antibody titer or T lymphocytes with disease severity as an outcome. Sixty-three studies were included in the final review.
RESULTS
RSV-specific antibody appears to protect from disease in mice, but such an effect was less evident in bovine RSV. Strong T-cell, Th1, Th2, Th17, CD4/CD8 responses, and weak Treg responses accompany severe disease in mice.
CONCLUSIONS
Murine studies suggest that measures of T-lymphocyte activity (particularly CD4 and CD8 T cells) may be predictive biomarkers of severity. Further inquiry is merited to validate these results and assess relevance as biomarkers for human disease.
Topics: Aged; Animals; Antibodies, Viral; Biomarkers; CD8-Positive T-Lymphocytes; Cattle; Humans; Infant; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 34522970
DOI: 10.1093/infdis/jiab370 -
The Journal of Infectious Diseases Aug 2022Respiratory syncytial virus related acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in adults with comorbidities. We aimed to identify all... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory syncytial virus related acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in adults with comorbidities. We aimed to identify all studies investigating the disease burden of RSV-ARI in this group.
METHODS
We estimated the incidence, hospitalization rate, and in-hospital case fatality ratio (hCFR) of RSV-ARI in adults with comorbidities based on a systematic review of studies published between January 1996 and March 2020. We also investigated the association between RSV-ARI and any comorbidity in adults. Meta-analyses based on random effects model were carried out.
RESULTS
Overall, 20 studies were included. The annual incidence rate of RSV-ARI in adults with any comorbidity was 37.6 (95% confidence interval [CI], 20.1-70.3) per 1000 persons per year in industrialized countries and the seasonal incidence rate was 28.4 (11.4-70.9) per 1000 persons per season. The hCFR in industrialized countries was 11.7% (5.8%-23.4%). There were no studies in developing countries. There were insufficient data to generate the meta-estimate of hospitalization rate. The likelihood of experiencing RSV-ARI for those with any comorbidity compared to those without was estimated to be 4.1 (odds ratio [OR], 1.6-10.4) and 1.1 (OR, 0.6-1.8) from studies using univariable and multivariable analysis respectively.
CONCLUSION
The disease burden of RSV-ARI among adults with comorbidity is substantial with limited data available.
Topics: Adult; Comorbidity; Cost of Illness; Hospitalization; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 34522961
DOI: 10.1093/infdis/jiab040 -
Influenza and Other Respiratory Viruses Nov 2021Several local studies showed that the 2009 influenza pandemic delayed the RSV season. However, no global-level analyses are available on the possible impact of the 2009...
BACKGROUND
Several local studies showed that the 2009 influenza pandemic delayed the RSV season. However, no global-level analyses are available on the possible impact of the 2009 influenza pandemic on the RSV season.
OBJECTIVES
We aim to understand the impact of the 2009 influenza pandemic on the RSV season.
METHODS
We compiled data from published literature (through a systematic review), online reports/datasets and previously published data on global RSV seasonality and conducted a global-level systematic analysis on the impact of the 2009 influenza pandemic on RSV seasonality.
RESULTS
We included 354 seasons of 45 unique sites, from 26 countries. Globally, the influenza pandemic delayed the onset of the first RSV season by 0.58 months on average (95% CI: 0.42, 0.73; maximum delay: 2.5 months) and the onset of the second RSV season by a lesser extent (0.25 months; 95% CI: 0.12, 0.39; maximum delay: 3.4 months); no delayed onset was observed for the third RSV season. The delayed onset was most pronounced in the northern temperate, followed by the southern temperate, and was least pronounced in the tropics.
CONCLUSIONS
The 2009 influenza pandemic delayed the RSV onset on average by 0.58 months and up to 2.5 months. This suggests evidence of viral interference as well as the impact of public health measures and has important implications for preparedness for RSV season during the ongoing COVID-19 pandemic and future pandemics.
Topics: COVID-19; Humans; Infant; Influenza, Human; Pandemics; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; SARS-CoV-2; Seasons
PubMed: 34219389
DOI: 10.1111/irv.12884 -
The Journal of Pediatrics Dec 2021To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.
OBJECTIVES
To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.
STUDY DESIGN
We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study.
RESULTS
We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%).
CONCLUSIONS
RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.
Topics: Adolescent; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Incidence; Infant; Male; Nervous System Diseases; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34181989
DOI: 10.1016/j.jpeds.2021.06.045 -
Vaccine Jun 2021Respiratory Syncytial Virus (RSV) is a common respiratory virus that generally causes a mild illness in children and adults or severe symptoms with complications in... (Review)
Review
Respiratory Syncytial Virus (RSV) is a common respiratory virus that generally causes a mild illness in children and adults or severe symptoms with complications in infants and the elderly, particularly in the presence of underlying comorbidities. While epidemiological data about this virus are available globally, data from the Middle East and North Africa (MENA) region are still scarce. For this reason, we conducted a systematic review to determine the burden of RSV disease in the MENA region by searching the available literature up until September 2018. A total of 1242 studies were retrieved of which 90 were included in the review. Most of the included studies were conducted in subjects aged 0-18 years with the majority being in children below 3 years of age, while only 2 studies included exclusively adults above 18 years of age. RSV infection rates varied greatly between different studies on hospitalized subjects and ranged between 4% and 82%, while the range was smaller in studies on outpatient subjects (between 6% and 36%). When calculating the RSV infection rates in the hospitalized subjects with different inclusion criteria, we found that it was 19%, 70%, and 33% among subjects admitted with Acute Respiratory Infections (ARIs), Acute Lower Respiratory Infections (ALRIs), and bronchiolitis, respectively. RSV infections were most common during the winter season. With regards to complications, intensive care unit admissions ranged between 1% and 15%, while the need for mechanical ventilation ranged between 1% and 10%. The overall RSV related mortality rate across all age groups in studies included in our review was 1.9%. This review identifies several limitations in the existing data and under-representation of the adult population. Future studies should be providing more evidence on the RSV burden in adults and children with comorbidities in order to better assess the potential impact of future preventive strategies in the MENA region.
Topics: Adolescent; Adult; Africa, Northern; Aged; Child; Hospitalization; Humans; Infant; Middle East; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34099329
DOI: 10.1016/j.vaccine.2021.05.076 -
Influenza and Other Respiratory Viruses Jul 2021Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking.
METHODS
This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as "Respiratory Syncytial Virus, Human," "Respiratory Syncytial Virus Infections," "Respiratory Syncytial Virus Vaccines," "Immunization," "Immunization Programs" and "Vaccines" and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV-associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case.
RESULTS
Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live-attenuated/chimeric (n = 14), recombinant-vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season.
CONCLUSION
LID ∆M2-2, MEDI M2-2, RSVcps2 and LID/∆M2-2 /1030s (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.
Topics: Aged; Antibodies, Neutralizing; Antibodies, Viral; Child; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccines, Attenuated
PubMed: 33764693
DOI: 10.1111/irv.12850 -
Epidemics Jun 2021Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development...
BACKGROUND
Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.
METHODS
We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies.
FINDINGS
Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries.
INTERPRETATION
The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.
Topics: Developing Countries; Humans; Models, Theoretical; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 33662812
DOI: 10.1016/j.epidem.2021.100444 -
The Journal of Infectious Diseases Aug 2022Respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (RSV-ALRTI) constitutes a substantial disease burden in young children. We aimed to... (Meta-Analysis)
Meta-Analysis
Risk Factors for Poor Outcome or Death in Young Children With Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infection: A Systematic Review and Meta-Analysis.
BACKGROUND
Respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (RSV-ALRTI) constitutes a substantial disease burden in young children. We aimed to identify all studies investigating the risk factors for RSV-ALRTI poor outcome or death in young children.
METHODS
We carried out a systematic literature review across 7 databases with data from studies published from January 1995 to December 2019. We defined poor outcome as need for prolonged hospital stay, oxygen supplementation, mechanical ventilation, or intensive care unit admission. The quality of all eligible studies was assessed according to modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. We conducted meta-analyses to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for individual risk factors.
RESULTS
We identified 27 eligible studies, which investigated 20 risk factors for RSV-ALRTI poor outcome and/or death in children <5 years old, compared with children with RSV-ALRTI who did not have poor outcome or who did not die. Among the risk factors, 6 were significantly associated with RSV-ALRTI poor outcome: any comorbid condition (OR, 2.69; 95% CI, 1.89-3.83), congenital heart disease (3.40; 2.14-5.40), prematurity with gestational age (GA) <37 weeks (1.75 (1.31-2.36), prematurity with GA ≤32 weeks (2.68; 1.43-5.04), age <3 months (4.91; 1.64-14.71), and age <6 months (2.02; 1.73-2.35). The meta-estimate ORs for all risk factors other than age <3 months were based on studies using multivariable analysis. For death, only prematurity with GA <37 weeks had a significant meta-estimated OR-3.81 (95% CI, 1.68-8.63)-based on univariable analysis.
CONCLUSIONS
This study represents a comprehensive report of the association between various risk factors and RSV-ALRTI poor outcome or death in young children. More research should be carried out to elucidate risk factors associated with poor outcome or death using multivariable analysis.
Topics: Child; Child, Preschool; Hospitalization; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Risk Factors
PubMed: 33576788
DOI: 10.1093/infdis/jiaa751 -
Nutrients Jan 2021Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs)....
Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are , respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms "vitamin D" and "" or "Respiratory Syncytial Virus" or "Influenza". A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Topics: Child; Child, Preschool; Cytokines; Humans; Immunity, Innate; Immunomodulation; Infant; Influenza A virus; Influenza, Human; Pneumonia, Pneumococcal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Vitamin D
PubMed: 33478006
DOI: 10.3390/nu13010276 -
PharmacoEconomics Mar 2021Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus...
Assessment of the Effects of Active Immunisation against Respiratory Syncytial Virus (RSV) using Decision-Analytic Models: A Systematic Review with a Focus on Vaccination Strategies, Modelling Methods and Input Data.
BACKGROUND
Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus (RSV).
METHODS
We searched MEDLINE, Embase, and SCOPUS and included model-based evaluations of RSV vaccinations. Two reviewers performed the selection, data extraction, and quality evaluation with EVIDEM. Cost-effectiveness (CE) estimates were converted to $US purchasing power parity (PPP), year 2018 values. Potential economic and epidemiological outcomes were summarised for maternal, infant, children, and elderly vaccinations. The PROSPERO identifier is CRD42019122570.
RESULTS
In total, 22 model-based studies were reviewed. On average, a potential 27% reduction in RSV hospitalisations in infants was projected for maternal vaccination and 50% for direct infant immunisation. The CE of maternal vaccination was $US1766-5857 PPP 2018/disability-adjusted life-years (DALYs) for Global Alliance for Vaccines and Immunisation (Gavi)-eligible countries. For England, the maximum cost-effective price of maternal vaccination was estimated at $US81.5 PPP 2018. Infant vaccination was associated with higher CE ratios in low- and high-income settings. Vaccination of neonates born before the RSV season was the most cost effective in high-income settings. Higher values for vaccine effectiveness, duration of protection, and vaccine uptake increased the benefits. Due to indirect effects, the vaccination of school-age children and a cocooning strategy were effective alternatives to protect infants, and the vaccination of children aged < 5 years had a beneficial impact on the elderly.
CONCLUSION
RSV vaccines with anticipated characteristics may reduce a sizeable proportion of the RSV burden. The results are subject to uncertainty because of the limited epidemiological and clinical data. Data on RSV incidence and hospitalisation risk for granular age strata should be prioritised to facilitate the evaluation of RSV interventions and decision making.
Topics: Aged; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Pregnancy; Quality-Adjusted Life Years; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccination
PubMed: 33462760
DOI: 10.1007/s40273-020-00991-7