scholarly journals Temporal Dysbiosis of Infant Nasal Microbiota Relative to Respiratory Syncytial Virus Infection

2020 ◽  
Author(s):  
Alex Grier ◽  
Ann L. Gill ◽  
Haeja A. Kessler ◽  
Anthony Corbett ◽  
Sanjukta Bandyopadhyay ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Disease ◽  
Disease Severity ◽  
Disease Risk ◽  
Developmental Trajectory ◽  
Microbiota Composition ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Impact ◽  
Nasal Microbiota

ABSTRACTRationaleRespiratory Syncytial Virus (RSV) infection is a leading cause of infant respiratory disease and hospitalization. Infant airway microbiota occupying the nasopharynx have been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease severity and infection susceptibility, are not well understood.ObjectivesTo characterize associations between the nasal microbiota and RSV infection before, during, and after infants’ first respiratory illness.MethodsNasal 16S rRNA microbial community profiling of two cohorts of infants in the first year of life: 1) a cross-sectional cohort of 89 RSV infected infants sampled during illness and 102 population matched healthy controls, and 2) an individually matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled at time points before, during, and after infection.Measurements and Main ResultsWe identified 12 taxa significantly associated with RSV infection. All 12 were differentially abundant during infection, with seven differentially abundant prior to infection, and eight differentially abundant after infection. Eight of these taxa were associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs. infected than of disease severity.ConclusionsOur findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with first-time RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and the impact of RSV infection on microbiota composition. Identified taxa represent appealing targets for additional translationally-oriented research.

scholarly journals Temporal Dysbiosis of Infant Nasal Microbiota Relative to Respiratory Syncytial Virus Infection

2020 ◽  
Author(s):  
Alex Grier ◽  
Ann L Gill ◽  
Haeja A Kessler ◽  
Anthony Corbett ◽  
Sanjukta Bandyopadhyay ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Disease ◽  
Disease Severity ◽  
Temporal Dynamics ◽  
Disease Risk ◽  
Developmental Trajectory ◽  
Microbiota Composition ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Nasal Microbiota

Abstract Rationale Respiratory Syncytial Virus (RSV) is a leading cause of infant respiratory disease. Infant airway microbiota has been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease susceptibility and severity, are unknown. Objectives Characterize temporal associations between microbiota and RSV infection before, during, and after infants’ first respiratory illness. Methods 16S rRNA microbiota profiling of two infant cohorts in the first year of life: 1) a cross-sectional cohort of 89 RSV infected infants sampled during illness and 102 matched healthy controls, and 2) a matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled before, during, and after infection. Results We identified 12 taxa significantly associated with RSV infection. All 12 taxa were differentially abundant during infection, with 8 associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs. infected than of disease severity. Conclusions Our findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and impact of RSV infection on microbiota composition.

scholarly journals Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus.

1988 ◽  
Vol 168 (3) ◽  
pp. 1163-1168 ◽  
Author(s):  
M J Cannon ◽  
P J Openshaw ◽  
B A Askonas
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cell Line ◽  
Respiratory Disease ◽  
Cytotoxic T Cells ◽  
Lung Pathology ◽  
Class I Mhc ◽  
Rsv Infection ◽  
Syncytial Virus

We have examined the function of class I MHC-restricted cytotoxic T cells in experimental respiratory syncytial virus (RSV) infection of BALB/c mice by transfer of T cell line MJC-A2 and CTL clone E8a into RSV-infected mice. The T cell line cleared pulmonary RSV infection within 5 d in persistently infected gamma-irradiated mice, but caused acute respiratory disease. This was only seen in infected mice and was often lethal after transfer of greater than 3 x 10(6) CTL. Lower numbers of CTL produced less severe disease but still cleared lung RSV, albeit over a longer time course (up to 10 d). Clearance of lung RSV in immunocompetent mice by the T cell line and CTL clone was again accompanied by acute and sometimes lethal respiratory disease. Bronchoalveolar lavage showed severe lung hemorrhage and frequent neutrophil efflux in mice with CTL-augmented disease.

scholarly journals Disability-adjusted Life Years for respiratory syncytial virus in children under 2 years

2020 ◽  
Author(s):  
jefferson buendia ◽  
Fernando Polack ◽  
Juana Patricia Sanchez Villamil
Keyword(s):  
Respiratory Syncytial Virus ◽  
Statistical Parameter ◽  
Epidemiological Surveillance ◽  
Years Of Life Lost ◽  
Disability Adjusted Life Years ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Impact

Abstract BACKGROUND: Respiratory syncytial virus infection is the leading cause of bronchiolitis in Colombia. There is growing evidence about the impact of Respiratory syncytial virus on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years for respiratory syncytial virus in children under 2 years in ColombiaMETHODS: Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10000 iterations was used to estimate each statistical parameter using the package DALY calculator in R. RESULTS: In 2019, 260 873 years of life (CI95% 208 180- 347 023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16 – 27).CONCLUSION: This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies, such as RSV vaccination, to reduce morbidity associated with RSV infection should be encouraged in our country.

scholarly journals Modelling the household-level impact of a maternal respiratory syncytial virus (RSV) vaccine in a high-income setting

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Patricia T. Campbell ◽  
Nicholas Geard ◽  
Alexandra B. Hogan
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccine Trial ◽  
Population Level ◽  
High Income ◽  
Demographic Model ◽  
Model Framework ◽  
Substantial Impact ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Impact

Abstract Background Respiratory syncytial virus (RSV) infects almost all children by the age of 2 years, with the risk of hospitalisation highest in the first 6 months of life. Development and licensure of a vaccine to prevent severe RSV illness in infants is a public health priority. A recent phase 3 clinical trial estimated the efficacy of maternal vaccination at 39% over the first 90 days of life. Households play a key role in RSV transmission; however, few estimates of population-level RSV vaccine impact account for household structure. Methods We simulated RSV transmission within a stochastic, individual-based model framework, using an existing demographic model, structured by age and household and parameterised with Australian data, as an exemplar of a high-income country. We modelled vaccination by immunising pregnant women and explicitly linked the immune status of each mother-infant pair. We quantified the impact on children for a range of vaccine properties and uptake levels. Results We found that a maternal immunisation strategy would have the most substantial impact in infants younger than 3 months, reducing RSV infection incidence in this age group by 16.6% at 70% vaccination coverage. In children aged 3–6 months, RSV infection was reduced by 5.3%. Over the first 6 months of life, the incidence rate for infants born to unvaccinated mothers was 1.26 times that of infants born to vaccinated mothers. The impact in older age groups was more modest, with evidence of infections being delayed to the second year of life. Conclusions Our findings show that while individual benefit from maternal RSV vaccination could be substantial, population-level reductions may be more modest. Vaccination impact was sensitive to the extent that vaccination prevented infection, highlighting the need for more vaccine trial data.

scholarly journals Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0131927 ◽  
Author(s):  
H. K. Brand ◽  
I. M. L. Ahout ◽  
D. de Ridder ◽  
A. van Diepen ◽  
Y. Li ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Rsv Infection ◽  
Syncytial Virus

scholarly journals The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis

2021 ◽  
Vol 17 (4) ◽  
pp. e1009529
Author(s):  
Thomas Démoulins ◽  
Melanie Brügger ◽  
Beatrice Zumkehr ◽  
Blandina I. Oliveira Esteves ◽  
Kemal Mehinagic ◽  
...  
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Disease Severity ◽  
Early Life ◽  
Cell Compartment ◽  
Neonatal Lung ◽  
Rsv Infection ◽  
Syncytial Virus

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.

Association of Viral Load With Disease Severity in Outpatient Children With Respiratory Syncytial Virus Infection

2020 ◽  
Vol 222 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Erika Uusitupa ◽  
Matti Waris ◽  
Terho Heikkinen
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Respiratory Infections ◽  
Respiratory Illness ◽  
Lower Viral Load ◽  
Primary Analysis ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Outpatient Children

Abstract Background There are scarce data on whether viral load affects the severity of respiratory syncytial virus (RSV) disease in outpatient children. Methods We analyzed the association between viral load and disease severity among children who participated in a prospective cohort study of respiratory infections. The children were examined and nasal swabs for the detection of RSV were obtained during each respiratory illness. Quantification of RSV load was based on the cycle threshold (Ct) value. For the primary analysis, the children were divided into 2 groups: higher (Ct < 27) and lower viral load (Ct ≥ 27). Results Among 201 episodes of RSV infection, children with higher viral load had significantly longer median durations of rhinitis (8 vs 6 days; P = .0008), cough (8 vs 6 days; P = .034), fever (2 vs 1 days; P = .018), and any symptom (10 vs 8 days; P = .024) than those with lower viral load. There were statistically significant negative correlations between the Ct values and durations of all measured symptoms. Conclusions Our findings support the concept that viral load drives the severity of RSV disease in children. Reducing the viral load by RSV antivirals might provide substantial benefits to outpatient children.

Immune profiles provide insights into respiratory syncytial virus disease severity in young children

2020 ◽  
Vol 12 (540) ◽  
pp. eaaw0268 ◽  
Author(s):  
Santtu Heinonen ◽  
Victoria M. Velazquez ◽  
Fang Ye ◽  
Sara Mertz ◽  
Santiago Acero-Bedoya ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Virus Disease ◽  
Severe Disease ◽  
Mild Disease ◽  
Hla Dr ◽  
Increased Risk ◽  
Determining Factors ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a “safe and protective” immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants.

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