Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure

Thwaites, Ryan S.; Coates, Matthew; Ito, Kazuhiro; Ghazaly, Marwa; Feather, Calandra; Abdulla, F.A.; Tunstall, Tanushree; Jain, Pooja; Cass, Lindsey; Rapeport, Garth; Hansel, Trevor T.; Nadel, Simon; Openshaw, Peter

doi:10.1164/rccm.201712-2567oc

Cited by 88 publications

(82 citation statements)

References 48 publications

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“…Information in regard to the dynamics of VL in infants with RSV infection is also limited, possibly due to the difficulty of performing daily sampling in these young children [10,26,27]. Two different studies of different sample sizes evaluated VL in children with RSV LRTI during the first 3 days of hospitalization or every other day during the first week of hospital stay.…”

Section: Discussionmentioning

confidence: 99%

Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection

Garcia-Maurino

Moore‐Clingenpeel

Thomas

et al. 2018

The Journal of Infectious Diseases

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Background. The association between respiratory syncytial virus (RSV) loads and clinical outcomes in children remains to be defined. In most studies, viral loads (VL) were evaluated in hospitalized children and at a single time-point. We investigated the relationship between VLs and disease severity in both outpatients and inpatients with RSV infection.Methods. We enrolled previously healthy children with RSV infection. Disease severity was defined by level of care (outpatients vs ward vs pediatric intensive care unit [PICU]), and a clinical disease severity score (CDSS). Nasopharyngeal VLs by polymerase chain reaction and CDSS were measured at enrollment and daily in inpatients. VL decay according to disease severity was analyzed using linear mixed modeling.Results. From February 2015 to March 2017, we enrolled 150 infants: 39 outpatients and 111 inpatients. VLs were higher in outpatients than in age-matched inpatients. Among inpatients, initial VLs were comparable in ward and PICU patients, and preceded the peak CDSS. However, after excluding infants treated with steroids, those hospitalized in the ward had higher VLs than infants requiring PICU care (P < .001). Dynamic analyses showed that VL decay was delayed in PICU patients, especially in those treated with steroids.Conclusions. Higher VLs at presentation and a faster and consistent VL decline were both associated with less severe RSV disease in children.

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Section: Discussionmentioning

confidence: 99%

Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection

Garcia-Maurino

Moore‐Clingenpeel

Thomas

et al. 2018

The Journal of Infectious Diseases

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“…As RSV has developed potent mechanisms to evade this innate interferon response, the virus is able to infect most infants through RSV-NS1/2 proteins inhibiting IRF-3 and STAT-2 reducing both IFN-I and INF-III responses and RSVF protein suppressing IRF-1 through EGRF activation. [44][45][46][47] While severe RSV bronchiolitis is associated with weaker antiviral innate interferon responses, data on the association between virus genome load and illness severity are discrepant. 47,48 Furthermore, ineffective inflammatory and adaptive immune responses are important factors that contribute to severe RSV disease.…”

Section: Rsv Infectionsmentioning

confidence: 99%

“…[44][45][46][47] While severe RSV bronchiolitis is associated with weaker antiviral innate interferon responses, data on the association between virus genome load and illness severity are discrepant. 47,48 Furthermore, ineffective inflammatory and adaptive immune responses are important factors that contribute to severe RSV disease. As at birth the immune system is still immature and needs to develop, it depends mostly on the innate immune system in response to toll-like receptor (TLR) ligation and maternal-derived antibodies.…”

Section: Rsv Infectionsmentioning

confidence: 99%

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Jartti

Smits

Bønnelykke

et al. 2018

Allergy

122

190

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Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.

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“…Inhibitory cytokines are also detected following RSV infection in mice, most commonly IL-10 [77,79]. Importantly, these same cytokines are elevated in the nasopharyngeal secretions of infants recently infected with RSV [73,[80][81][82]. The induction of many pro-inflammatory cytokines has been directly associated with CD8 T cell responses.…”

Section: Cd8 T Cell Cytokine Productionmentioning

confidence: 99%

“…RSV infection induces the production of IFN-γ in the nasal passages and serum of infants, and the levels are elevated above what is observed in healthy infants [80,92]. However, IFN-γ levels in the blood, serum, or nasal washes of infants exhibiting severe RSV disease are substantially reduced compared to infants with only mild RSV disease [80,82,93]. One example of this dichotomy is that infants requiring mechanical ventilation following RSV infection exhibit significantly reduced nasal IFN-γ protein levels versus RSV-infected infants not requiring mechanical ventilation [94].…”

Section: Ifn-γmentioning

confidence: 99%

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

Schmidt

Varga

2020

Cytokine

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection and hospitalization in infants. In spite of the enormous clinical burden caused by RSV infections, there remains no efficacious RSV vaccine. CD8 T cells mediate viral clearance as well as provide protection against a secondary RSV infection. However, RSV-specific CD8 T cells may also induce immunopathology leading to exacerbated morbidity and mortality. Many of the crucial functions performed by CD8 T cells are mediated by the cytokines they produce. IFN-γ and TNF are produced by CD8 T cells following RSV infection and contribute to both the acceleration of viral clearance and the induction of immunopathology. To prevent immunopathology, regulatory mechanisms are in place within the immune system to inhibit CD8 T cell effector functions after the infection has been cleared. The actions of a variety of cytokines, including IL-10 and IL-4, play a critical role in the regulation of CD8 T cell effector activity. Herein, we review the current literature on CD8 T cell responses and the functions of the cytokines they produce following RSV infection. Additionally, we discuss the regulation of CD8 T cell activation and effector functions through the actions of various cytokines.

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Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure

Cited by 88 publications

References 48 publications

Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection

Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

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