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.

scholarly journals Fcγ Receptor IIa (FCGR2A) Polymorphism Is Associated With Severe Respiratory Syncytial Virus Disease in Argentinian Infants

2020 ◽  
Vol 10 ◽  
Author(s):  
María Pía Holgado ◽  
Silvina Raiden ◽  
Inés Sananez ◽  
Vanesa Seery ◽  
Leonardo De Lillo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Disease ◽  
Severe Disease ◽  
Critical Role ◽  
Fcγ Receptor ◽  
Factors Associated ◽  
Severe Group ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Relationship

BackgroundMost patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease.MethodsBlood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied.ResultsGenotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3.ConclusionsWe found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization.

scholarly journals Epidemiologic, Experimental, and Clinical Links between Respiratory Syncytial Virus Infection and Asthma

2008 ◽  
Vol 21 (3) ◽  
pp. 495-504 ◽  
Author(s):  
Shyam S. Mohapatra ◽  
Sandhya Boyapalle
Keyword(s):  
Respiratory Syncytial Virus ◽  
Childhood Asthma ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Severe Disease ◽  
Infection Process ◽  
Increased Risk ◽  
Rsv Infection ◽  
Recurrent Wheeze ◽  
Syncytial Virus

SUMMARY Virtually all children experience respiratory syncytial virus (RSV) infection at least once during the first 2 years of life, but only a few develop bronchiolitis and more severe disease requiring hospitalization, usually in the first 6 months of life. Children who recover from RSV-induced bronchiolitis are at increased risk for the development of recurrent wheeze and asthma in later childhood. Recent studies suggest that there is an association between RSV-induced bronchiolitis and asthma within the first decade of life but that this association is not significant after age 13. Despite the considerable progress made in our understanding of several aspects of respiratory viral infections, further work needs to be done to clarify the molecular mechanisms of early interactions between virus and host cell and the role of host gene products in the infection process. This review provides a critical appraisal of the literature in epidemiology and experimental research which links RSV infection to asthma. Studies to date demonstrate that there is a significant association between RSV infection and childhood asthma and that preventing severe primary RSV infections can decrease the risk of childhood asthma.

scholarly journals Antibody Responses to Respiratory Syncytial Virus: A Cross-Sectional Serosurveillance Study in the Dutch Population Focusing on Infants Younger Than 2 Years

2020 ◽  
Author(s):  
Guy Berbers ◽  
Liesbeth Mollema ◽  
Fiona van der Klis ◽  
Gerco den Hartog ◽  
Rutger Schepp
Keyword(s):  
Respiratory Syncytial Virus ◽  
Chronic Obstructive ◽  
Igg Antibody ◽  
Cross Sectional ◽  
Mild Disease ◽  
Copd Patients ◽  
Increased Risk ◽  
Iga Antibodies ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) generally causes mild disease but can cause severe infections in (premature) infants and elderly adults. Here, we studied RSV-specific antibody concentrations throughout life with emphasis on infants and chronic obstructive pulmonary disease (COPD) patients. Methods Sera (N = 2655) from 2 nationwide cross-sectional studies in the Netherlands including individuals aged 0–90 years were analyzed for IgG and IgA antibodies to RSV prefusion F, postfusion F, N, Ga, and Gb proteins and for antibody avidity in 42 COPD patients. Results Maternal IgG concentrations declined to age 10–12 months. After the first year of life, approximately 40% of children lacked infection-induced IgA antibodies and may therefore be uninfected. All Dutch children showed serological evidence of RSV infection by age 3 years. Antibody concentrations reached a plateau by age 5–9 years and remains constant throughout life. COPD patients had similar levels and avidity of RSV-specific IgG antibodies compared with age-matched healthy controls. Conclusions RSV-IgG antibody patterns throughout life can be used to estimate the degree of immunity acquisition to RSV and to identify groups at increased risk of infection. Seroprevalence of IgA could be a proxy to determine RSV infection in children younger than 1 year.

scholarly journals Respiratory syncytial virus and airway microbiota -- A complex interplay and its reflection on morbidity

2020 ◽  
Author(s):  
Giovanni Rossi ◽  
Stefania Ballarini ◽  
Michela Silvestri ◽  
Oliviero Sacco ◽  
Andrew Colin
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Respiratory Infections ◽  
Pediatric Population ◽  
Bacterial Species ◽  
Severe Disease ◽  
Microbial Community Composition ◽  
Positive Role ◽  
Syncytial Virus ◽  
Tract Infections

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV, can also increase the virulence of potential pathogens in nasopharynx, which is a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Negative changes in microbial community composition in early life may constitute a heightened risk towards severe RSV respiratory infection and bacterial superinfection, whilst specific groups of microorganisms can be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species in disease prevention as well as into the possible benefits of microbiome therapeutic manipulation, may improve patient outcomes.

scholarly journals Respiratory Syncytial Virus Prophylaxis in Special Populations: Is it Something Worth Considering in Cystic Fibrosis and Immunosuppression?

2011 ◽  
Vol 16 (2) ◽  
pp. 77-86
Author(s):  
William A. Prescott ◽  
David J. Hutchinson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cost Benefit ◽  
The United States ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Cost ◽  
Infant Hospitalization ◽  
Infants And Young Children

ABSTRACT Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of infant hospitalization in the United States. Prophylaxis with palivizumab is effective in reducing RSV hospitalizations in premature infants and in infants or children with chronic lung disease or congenital heart disease. Patients with CF or those who are immunocompromised may be at increased risk for RSV infection–related complications; hence, prophylaxis may prove beneficial to these populations. The extent of palivizumab use in the CF and immunocompromised populations is variable. Palivizumab appears to be safe and may be effective in infants and young children with CF and immunocompromise. However, well-designed, randomized, controlled trials published in peer-reviewed journals are lacking, and its routine use can therefore not be recommended at this time. If used in patients with CF or those who are immunocompromised, RSV prophylaxis should be restricted to peak outbreak months in order to optimize the cost benefit of palivizumab.

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 Respiratory Syncytial Virus Disease Severity in Young Children

2020 ◽  
Author(s):  
Zaid Haddadin ◽  
Stockton Beveridge ◽  
Kailee Fernandez ◽  
Danielle A Rankin ◽  
Varvara Probst ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Young Children ◽  
Disease Severity ◽  
Severity Score ◽  
Respiratory Infections ◽  
Virus Disease ◽  
Younger Age ◽  
Inpatient Settings ◽  
Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections (ARIs) in hospitalized children. Although prematurity and underlying medical conditions are known risk factors, most of these children are healthy, and factors including RSV load and subgroups may contribute to severity. Therefore, we aimed to evaluate the role of RSV in ARI severity and determine factors associated with increased RSV-ARI severity in young children. Methods Children aged &lt;5 years with fever and/or ARI symptoms were recruited from the emergency department (ED) or inpatient settings at Vanderbilt Children’s Hospital. Nasal and/or throat swabs were tested using quantitative reverse-transcription polymerase chain reaction for common respiratory viruses, including RSV. A severity score was calculated for RSV-positive children. Results From November 2015 through July 2016, 898 participants were enrolled, and 681 (76%) had at least 1 virus detected, with 191 (28%) testing positive for RSV. RSV-positive children were more likely to be hospitalized, require intensive care unit admission, and receive oxygen compared with children positive for other viruses. Higher viral load, White race, younger age, and higher severity score were independently associated with hospitalization in RSV-positive children. No differences in disease severity were noted between RSV A and RSV B. Conclusions RSV was associated with increased ARI severity in young children enrolled from the ED and inpatient settings, but no differences in disease severity were noted between RSV A and RSV B. These findings emphasize the need for antiviral therapy and/or preventive measures such as vaccines against RSV in young children.

scholarly journals Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8+ T-Cell Profiles

2020 ◽  
Vol 201 (3) ◽  
pp. 325-334 ◽  
Author(s):  
David T. Siefker ◽  
Luan Vu ◽  
Dahui You ◽  
Andrew McBride ◽  
Ryleigh Taylor ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Disease Severity ◽  
Virus Disease ◽  
Cd8 T Cell ◽  
Respiratory Syncytial Virus Disease ◽  
Syncytial Virus

scholarly journals Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
D. C. Busse ◽  
D. Habgood-Coote ◽  
S. Clare ◽  
C. Brandt ◽  
I. Bassano ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Severe Disease ◽  
Early Time ◽  
Airway Epithelial Cells ◽  
Knockout Mouse Model ◽  
Antiviral Genes ◽  
Wide Range ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Cellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defense. We have previously used a bioinformatic screen to identify two interferon-stimulated genes (ISG) with poorly characterized function, interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in respiratory syncytial virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model, we investigated the antiviral capability of these genes in the control of RSV replication. Overexpression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time postinfection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss of Ifi44 was associated with a more severe infection phenotype in a mouse model of infection. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection. IMPORTANCE RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.

scholarly journals Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

2014 ◽  
Vol 45 (3) ◽  
pp. 718-725 ◽  
Author(s):  
Corné H. van den Kieboom ◽  
Inge M.L. Ahout ◽  
Aldert Zomer ◽  
Kim H. Brand ◽  
Ronald de Groot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Pathogen Detection ◽  
Severe Disease ◽  
Host Gene ◽  
Host Gene Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections.

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