Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis

Brand, H. Kim; Groot, Ronald de; Galama, J.M.D.; Brouwer, Marianne; Teuwen, Karin; Hermans, Peter W. M.; Melchers, Willem J. G.; Warris, Adilia

doi:10.1002/ppul.21552

Cited by 111 publications

(167 citation statements)

References 32 publications

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“…[2][3][4][5] Indeed, HRV infections are one of the main causes of bronchiolitis in young children and an inducer of wheezing episodes. [6][7][8][9] Factors involved in increased disease severity in HRV infections are contradicting in the literature. Some reports have associated coinfection with a second respiratory viruswith a more severe disease, 10,11 whereas others have not.…”

Section: What This Study Addsmentioning

confidence: 55%

“…12 Underlying risk conditions may also be involved in disease severity. 9,13 Again, the reports are contradicting; atopic family history has been associated with severe HRV infection, whereas exposure to smoking has not, 11 and the opposite has been reported in another study. 9 Furthermore, congenital heart disease was considered a risk factor in 1 study 3 but not in another.…”

Section: What This Study Addsmentioning

confidence: 58%

“…9,13 Again, the reports are contradicting; atopic family history has been associated with severe HRV infection, whereas exposure to smoking has not, 11 and the opposite has been reported in another study. 9 Furthermore, congenital heart disease was considered a risk factor in 1 study 3 but not in another. 9 Recently, our group evaluated the role of HRV coinfections in children with LRTI and observed no significant difference in frequencies of severe infections caused by HRV in single or coinfections.…”

Section: What This Study Addsmentioning

confidence: 58%

“…Some reports have associated coinfection with a second respiratory viruswith a more severe disease, 10,11 whereas others have not. 7,9 On the other hand, another study has raised the possibility of a protective role of HRV against other viral infections. 12 Underlying risk conditions may also be involved in disease severity.…”

Section: What This Study Addsmentioning

confidence: 99%

“…9 Furthermore, congenital heart disease was considered a risk factor in 1 study 3 but not in another. 9 Recently, our group evaluated the role of HRV coinfections in children with LRTI and observed no significant difference in frequencies of severe infections caused by HRV in single or coinfections. 14 However, the investigation was carried out only with LRTI cases.…”

Section: What This Study Addsmentioning

confidence: 99%

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Human Rhinovirus and Disease Severity in Children

Costa¹,

Queiróz²,

Silveira

et al. 2014

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT: Human rhinovirus has been known as the common cold agent. Recently, studies have reported that this virus is responsible for severe infections of the lower respiratory tract in children. Reports of factors that increase disease severity have been contradictory. WHAT THIS STUDY ADDS:This study identifies some of the factors involved in disease severity in HRV infections in children. We expect that children at risk for developing severe disease could be identified sooner and appropriate measures could be taken. abstract OBJECTIVE: To evaluate retrospectively human rhinovirus (HRV) infections in children up to 5 years old and factors involved in disease severity.METHODS: Nasopharyngeal aspirates from 434 children presenting a broad range of respiratory infection symptoms and severity degrees were tested for presence of HRV and 8 other respiratory viruses. Presence of host risk factors was also assessed.RESULTS: HRV was detected in 181 (41.7%) samples, in 107 of them as the only agent and in 74 as coinfections, mostly with respiratory syncytial virus (RSV; 43.2%). Moderate to severe symptoms were observed in 28.9% (31/107) single infections and in 51.3% (38/74) coinfections (P = .004). Multivariate analyses showed association of coinfections with lower respiratory tract symptoms and some parameters of disease severity, such as hospitalization. In coinfections, RSV was the most important virus associated with severe disease. Prematurity, cardiomyopathies, and noninfectious respiratory diseases were comorbidities that also were associated with disease severity (P = .007).CONCLUSIONS: Our study showed that HRV was a common pathogen of respiratory disease in children and was also involved in severe cases, causing symptoms of the lower respiratory tract. Severe disease in HRV infections were caused mainly by presence of RSV in coinfections, prematurity, congenital heart disease, and noninfectious respiratory disease. Pediatrics 2014;133:e312-e321 AUTHORS:

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Section: What This Study Addsmentioning

confidence: 55%

Section: What This Study Addsmentioning

confidence: 58%

Section: What This Study Addsmentioning

confidence: 58%

Section: What This Study Addsmentioning

confidence: 99%

Section: What This Study Addsmentioning

confidence: 99%

See 3 more Smart Citations

Human Rhinovirus and Disease Severity in Children

Costa¹,

Queiróz²,

Silveira

et al. 2014

Pediatrics

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Respiratory syncytial virus infection augments NOD2 signaling in an IFN‐β‐dependent manner in human primary cells

et al. 2012

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Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants, with remarkable variability in disease severity. An exaggerated proinflammatory response and influx of leukocytes is part of the pathogenesis of severe RSV disease. Here, we show an increase in proinflammatory cytokine production by human immune cells after stimulation with RSV and muramyl dipeptide (MDP), which is recognized by nucleotide‐binding oligomerization domain containing 2 (NOD2). PBMCs from Crohn's disease patients homozygous for the 3020insC mutation in the NOD2 gene did not show a synergistic response to stimulation with RSV and MDP, suggesting that NOD2 is essential for the observed synergy. Further experiments aimed at identifying the viral ligand indicated that viral RNA plays an essential role in the recognition of RSV. Stimulation with RSV or Poly(I:C) induced IFN‐β expression, which resulted in an increased expression of the viral receptors TLR3 and RIG‐I, as well as an increased NOD2 expression. Our data indicate that IFN‐β induction by viral RNA is an essential first step in the increased proinflammatory response to MDP. We hypothesize that the enhanced proinflammatory response to MDP following RSV infection may be an important factor in determining the outcome of the severity of disease.

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The impact of viral dynamics on the clinical severity of infants with respiratory syncytial virus bronchiolitis

Zhou

Xiao

Zhao

et al. 2015

Journal of Medical Virology

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The impact of dynamic respiratory syncytial virus (RSV) load on the clinical severity of hospitalized infants with bronchiolitis has not been clarified. Nasopharyngeal aspirates were obtained from 60 infants who were diagnosed with bronchiolitis within 96 hr of wheezing onset upon admission and on days 3, 5, and 7 in the hospital, and 17 respiratory viruses were detected. The RSV load was quantified by real-time qPCR for RSV subtypes A and B at different time points. Scoring criteria were used to evaluate the degree of severity. A total of 40 infants were determined to be RSV-positive, nine were identified as RSV subtype A (RSVA), and 31 were RSV subtype B (RSVB). The peak RSV load was observed upon admission, and the RSV load decreased significantly over time; in addition, this decrease began to have significant differences on day 5. There was a positive correlation between the RSV load and the clinical score (r(2) = 0.121 and P < 0.001). According to the clinical scores, the infants in the severe group tended to have higher RSV loads than those in the moderate and mild groups. Multivariate logistic regression models revealed that the viral load on day 3 was independently associated with the degree of severity. This study elucidated that a higher mean RSV load was associated with a more severe disease and a longer duration of hospitalization and symptoms. This study also clarified RSV replication in infants and provides a theoretical basis for specifying an anti-RSV therapy strategy.

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Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis

Abstract: Disease severity in children with bronchiolitis is not associated with infection by multiple viruses. We conclude that other factors, such as age, contribute to disease severity to a larger extent.

Cited by 111 publications

References 32 publications

Human Rhinovirus and Disease Severity in Children

Human Rhinovirus and Disease Severity in Children

Respiratory syncytial virus infection augments NOD2 signaling in an IFN‐β‐dependent manner in human primary cells

The impact of viral dynamics on the clinical severity of infants with respiratory syncytial virus bronchiolitis

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