scholarly journals Altered Gut Microbiota in Infants is Associated with Respiratory Syncytial Virus Disease Severity

2020 ◽  
Author(s):  
Jeffrey Harding ◽  
David Siefker ◽  
Luan Vu ◽  
Dahui You ◽  
John Devincenzo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Virus Disease ◽  
Healthy Controls ◽  
Microbial Composition ◽  
16S Sequencing ◽  
Microbial Profile ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Rationale Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. There are still no vaccines or specific antiviral therapies against RSV, mainly due to the inadequate understanding of RSV pathogenesis. Recent data suggest a role for gut microbiota community structure in determining RSV disease severity.Objectives Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify future at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection.Methods We enrolled 58 infants hospitalized with RSV, 5 were admitted to the pediatric intensive care unit and thus considered severe, 53 were admitted to the pediatric ward and considered moderate, and 37 healthy controls collected from infants during “well-baby checkups” from 2012 to 2015. We evaluated the composition of gut microbiota within 72 hours of enrollment in these patients via 16s sequencing of fecal DNA.Measurements and Main Results There was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV vs. controls. Patients with severe RSV disease had slightly lower alpha diversity (richness and evenness of the bacterial community) of the gut microbiota compared to patients with moderate RSV and healthy controls. Beta diversity (overall microbial composition) was significantly different between all RSV patients (severe and moderate) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and Severe RSV). Conclusions Collectively, these data indicate that a unique gut microbial profile that is associated with severe RSV disease. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.

scholarly journals Altered Gut Microbiota in Infants is Associated with Respiratory Syncytial Virus Disease Severity

2020 ◽  
Author(s):  
Jeffrey Harding ◽  
David Siefker ◽  
Luan Vu ◽  
Dahui You ◽  
John Devincenzo ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Respiratory Syncytial Virus ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Pediatric Intensive Care Unit ◽  
Pediatric Intensive Care ◽  
Microbial Composition ◽  
Microbial Profile ◽  
Syncytial Virus

Abstract Background :Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. There are still no vaccines or specific antiviral therapies against RSV, mainly due to the inadequate understanding of RSV pathogenesis. Recent data suggest a role for gut microbiota community structure in determining RSV disease severity. Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection. Results : We enrolled 95 infants from Le Bonheur during the 2012 to 2015 RSV season. Of these, 37 were well-babies and 58 were hospitalized with RSV. Of the RSV infected babies, 53 remained in the pediatric ward (moderate) and 5 were moved to the pediatric intensive care unit at a later date (severe). Stool samples were collected within 72 hours of admission; and the composition of gut microbiota was evaluated via 16S sequencing of fecal DNA. There was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV (moderate and severe) vs. controls. Patients with severe RSV disease had slightly lower alpha diversity (richness and evenness of the bacterial community) of the gut microbiota compared to patients with moderate RSV and healthy controls. Beta diversity (overall microbial composition) was significantly different between all RSV patients (moderate and severe) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and severe RSV). Conclusions : Collectively, these data demonstrate that a unique gut microbial profile is associated with RSV disease and with severe RSV disease with admission to the pediatric intensive care unit. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.

scholarly journals Altered Gut Microbiota in Infants is Associated with Respiratory Syncytial Virus Disease Severity

2020 ◽  
Author(s):  
Jeffrey Harding ◽  
David Siefker ◽  
Luan Vu ◽  
Dahui You ◽  
John Devincenzo ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Respiratory Syncytial Virus ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Pediatric Intensive Care Unit ◽  
Pediatric Intensive Care ◽  
Microbial Composition ◽  
Microbial Profile ◽  
Syncytial Virus

Abstract RationaleRespiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. There are still no vaccines or specific antiviral therapies against RSV, mainly due to the inadequate understanding of RSV pathogenesis. Recent data suggest a role for gut microbiota community structure in determining RSV disease severity.ObjectivesOur objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection.MethodsWe enrolled 58 infants hospitalized with RSV, all were admitted to the pediatric ward. 53 remained in the pediatric ward (moderate) and 5 were moved to the pediatric intensive care unit at a later date (severe). We also enrolled 37 healthy infants during their “well-baby checkups” from 2012 to 2015. We evaluated the composition of gut microbiota from stool samples collected within 72 hours of enrollment via 16s sequencing of fecal DNA.Measurements and Main ResultsThere was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV (moderate and severe) vs. controls. Patients with severe RSV disease had slightly lower alpha diversity (richness and evenness of the bacterial community) of the gut microbiota compared to patients with moderate RSV and healthy controls. Beta diversity (overall microbial composition) was significantly different between all RSV patients (moderate and severe) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and severe RSV).ConclusionsCollectively, these data demonstrate that a unique gut microbial profile is associated with severe RSV disease prior to admission to the pediatric intensive care unit. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.

scholarly journals Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jeffrey N. Harding ◽  
David Siefker ◽  
Luan Vu ◽  
Dahui You ◽  
John DeVincenzo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Virus Disease ◽  
Respiratory Syncytial Virus Disease ◽  
Syncytial Virus

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 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 <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

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.

Sign in / Sign up

Export Citation Format

Share Document