scholarly journals Respiratory Syncytial Virus Infections Induce Hypermetabolism in Pediatric Upper Airways

2020 ◽  
Author(s):  
Svetlana Rezinciuc ◽  
Lavanya Bezavada ◽  
Azadeh Bahadoran ◽  
Jesse F. Ingels ◽  
Young-Yin Kim ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Glucose Uptake ◽  
Pediatric Patients ◽  
Upper Airway ◽  
Human Metabolism ◽  
Upper Airways ◽  
Rsv Infection ◽  
Respiratory Cells ◽  
Upper Respiratory ◽  
Syncytial Virus

AbstractTo determine whether respiratory syncytial virus (RSV) regulates human metabolism, we used positron emission tomography (PET) of patient lungs along with bioenergetics and metabolomics of patient upper airway cells and fluids. We previously found a significant negative monotonic relationship between glucose uptake and respiratory viral infection in 20 pediatric patients (e.g., 70% of infected patients had glucose uptake within 0–3 days). In our recent study, 3 out of 4 patients positive for glucose uptake at later times (>5 days) were positive for RSV infection. At present, the bioenergetics of upper respiratory cells (URCs) from nasal pharyngeal aspirates have not been investigated, and in vitro studies indicate RSV reduces metabolism in cell lines. To define metabolic changes in RSV-infected pediatric patients, we acquired fresh aspirates from 6 pediatric patients. Immediately following aspiration of URCs, we measured the two major energy pathways using an XFe flux analyzer. Glycolysis and mitochondrial respiration were significantly increased in URCs from RSV-infected patients, and mitochondrial respiration was operating at near maximal levels, resulting in loss of cellular capacity to increase respiration with impaired coupling efficiency. Metabolomics analysis of metabolites flushed from the upper airways confirmed a significant increase in TCA cycle intermediates. Taken together, these studies demonstrate RSV induces significant hypermetabolism in pediatric patients’ lungs and respiratory tract. Thus, hypermetabolism is a potential anti-viral drug target and reveals RSV can regulate human metabolism.Contributions to the fieldMetabolic changes in humans in response to viral infection are largely unknown. In this brief clinical report, we find metabolism is markedly increased in live upper respiratory cells from infants infected with respiratory syncytial virus (RSV) concomitant to changes in metabolites in their upper airway fluids. This sheds light on viral induced hypermetabolism in the airways and offers potential biomarkers for RSV. In addition, this identifies potential therapeutic targets for host directed therapies of aberrant metabolism in RSV. This work has clinical impact as biomarkers and therapeutics for RSV are needed for this pervasive virus that causes infections with long term consequence for some children. Further, advancements in molecular mechanisms underpinning RSV infection biology are constrained by the difficulties in translating model systems to humans as well as relating human studies in adults to infants (Mestas and Hughes, 2004; Papin et al., 2013).

scholarly journals Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

2005 ◽  
Vol 79 (10) ◽  
pp. 6035-6042 ◽  
Author(s):  
Negin Gitiban ◽  
Joseph A. Jurcisek ◽  
Randall H. Harris ◽  
Sara E. Mertz ◽  
Russell K. Durbin ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Upper Airway ◽  
Upper Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM.

Respiratory Syncytial Virus Infection Outbreak and Successful Treatment with IVIG and Oral Ribavirin among Pediatric Patients with Oncologic Diseases and/or BMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5267-5267
Author(s):  
Sema S. Anak ◽  
Didem Atay ◽  
Mesut Garipardic ◽  
Beril Ozalp ◽  
Diana Yani ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Symptoms ◽  
Pediatric Patients ◽  
Chronic Gvhd ◽  
Oncology Patients ◽  
Hyper Igm Syndrome ◽  
Rsv Infection ◽  
Hyper Igm ◽  
Syncytial Virus ◽  
Oncologic Diseases

Abstract Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy together with or without autologous/allogeneic stem cell transplantation (APBSCT), but there have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. Between February 20 – April 15, 2006, among 15 pediatric patients hospitalized for various oncologic diseases and post-BMT problems, 7 patients developed progressive cough and/or dyspnea. A survey of respiratory viruses was done using direct immunofluorescent antibody assay. Three patients (two high-risk patients with acute lymphoblastic leukemia receiving induction or consolidation chemotherapy, one under treatment for chronic GvHD postBMT) were found positive for RSV (20%). The remaining patients with respiratory symptoms were followed-up for RSV infection, but remained negative during all surveys. Three patients and the sister of the boy with hyper-IgM syndrome, who was also transplanted for hyper-IgM syndrome and under treatment for chronic GvHD and pneumonia, in the same room with her brother, were all treated with IVIG and specific antiviral therapy, oral Ribavirin (20–25 mg/kg/day in three doses). All patients recovered fully, although two were retreated due to recurrent RSV positivity and respiratory symptoms within two weeks. In striking contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in postBMT period, is very low and can easily be treated with IVIG and oral Ribavirin, used effectively because of unavailability of other forms (iv or nebulized forms) in our country, if diagnosed and treated early enough. It is even possible to give the scheduled anti-neoplastic therapy for not being delayed.

scholarly journals Comparison of Intravenous Palivizumab and Standard of Care for Treatment of Respiratory Syncytial Virus Infection in Mechanically Ventilated Pediatric Patients

2016 ◽  
Vol 21 (2) ◽  
pp. 146-154 ◽  
Author(s):  
Brady J. Helmink ◽  
Carolyn E. Ragsdale ◽  
Evan J. Peterson ◽  
Kathryn G. Merkel
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Treatment Group ◽  
Length Of Stay ◽  
Pediatric Patients ◽  
Standard Of Care ◽  
Hospital Length Of Stay ◽  
End Points ◽  
Rsv Infection ◽  
Syncytial Virus

OBJECTIVES: Evidence suggests palivizumab may be beneficial for respiratory syncytial virus (RSV) infection in pediatric patients, although it is only approved by the US Food and Drug Administration for RSV prophylaxis. The objective of this study is to compare outcomes among pediatric patients with RSV infection who received intravenous palivizumab and standard of care versus standard of care alone. METHODS: This is a retrospective, single-center cohort study conducted between November 2003 and October 2013. Pediatric patients with active RSV infection treated with intravenous (IV) palivizumab after initiation of mechanical ventilation were matched 1:1 to a control selected from ventilated patients who received standard of care. The primary end point evaluated the duration of mechanical ventilation between groups. Secondary end points included hospital length of stay, intensive care unit length of stay, duration of respiratory support over baseline, time to RSV microbiologic cure, duration of antibiotic therapy, and in-hospital mortality. RESULTS: A total of 22 patients with a median age of 3 months were included in the study. Patients in the treatment group received a median of 2 doses of IV palivizumab, with a mean dose of 14.2 mg/kg. All patients received bronchodilators and corticosteroids, with the exception of 1 patient in the control group, and only 1 treatment group patient received IV ribavirin. Duration of mechanical ventilation was longer in the treatment group (18.9 ± 9.5 vs. 14.3 ± 9.3 days; p = 0.26). No statistically significant differences were observed between groups for any of the secondary end points. CONCLUSIONS: Pediatric patients who received IV palivizumab in addition to standard of care for treatment of RSV infection following initiation of mechanical ventilation experienced similar outcomes to those who received standard of care alone. Further studies are necessary to evaluate the potential benefit of IV palivizumab in addition to current standard of care.

Serious Respiratory Tract Disease Caused by Respiratory Syncytial Virus: Prospects for Improved Therapy and Effective Immunization

PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 137-143
Author(s):  
Robert M. Chanock ◽  
Robert H. Parrott ◽  
Mark Connors ◽  
Peter L. Collins ◽  
Brian R. Murphy
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Durable Resistance ◽  
Secretory Iga ◽  
Upper Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus

On this felicitous occasion we honor Dr Saul Krugman for his many contributions to the study and control of a wide variety of important pediatric viral diseases. In preparing our remarks we found it difficult to identify a major pediatric viral pathogen upon which Saul had not left his mark. One of the few that escaped, for reasons unknown, is respiratory syncytial virus (RSV). Since RSV is the major pediatric respiratory tract viral pathogen, we thought this agent might pique his interest. Those of us studying RSV need all the help we can receive from biomedical scientists of Saul's caliber. What follows is a summary of current efforts to develop improved therapy and effective immunoprophylaxis for this elusive respiratory tract viral pathogen. IMMUNITY TO RSV DISEASE The mechanisms by which the immune system protects the respiratory tract against RSV infection and disease are not completely understood. However, it is clear that infection (or reinfection) induces resistance in the upper respiratory tract that is neither complete nor long lasting.1,2 The situation is some-what more favorable in the lower respiratory tract, where infection (or reinfection) induces more substantial and more durable resistance to disease. As a consequence, cumulative immunity from multiple reinfections protects older children and adults against the more serious forms of disease involving the lower respiratory tract such as bronchiolitis and pneumonia. Resistance to RSV infection in the upper respiratory tract appears to be mediated primarily by local secretory IgA antibodies, which explains the transitory nature of immunity in this region.3

scholarly journals The Prevention of Respiratory Syncytial Virus Infection in Children: Focus on Palivizumab

2009 ◽  
Vol 1 ◽  
pp. CMT.S2072
Author(s):  
Michael E. Speer ◽  
Amy B. Good
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
The United States ◽  
Humanized Monoclonal Antibody ◽  
Post Marketing ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
One Year ◽  
High Risk Infants

Recurrent upper respiratory infections caused by respiratory syncytial virus (RSV) and other respiratory viruses occur throughout life. During the first 2 years of life, RSV infected children have up to a 40% risk of a lower respiratory tract infection (LRTI). In turn LRTI, including bronchiolitis, due to RSV is the most common cause of hospitalization among infants less than one year of age. While mortality from RSV infection has fallen over the last 2 decades, approximately 400-500 deaths occur annually in the United States again primarily in infants less than 1 year of age. Palivizumab, a humanized monoclonal antibody, has been shown to reduce the risk of hospitalization in high risk infants if given monthly during RSV season. Post marketing safety surveillance originating from a variety of sources, mostly active surveillance, has confirmed the prelicensure safety profile of palivizumab. Other than very rare anaphylactic reactions (<1/100000), no significant adverse reactions have been noted.

scholarly journals Study protocol: a multicenter, uncontrolled, open-label study of palivizumab in neonates, infants, and preschool children at high risk of severe respiratory syncytial virus infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masaaki Mori ◽  
Shinichi Watabe ◽  
Tomoaki Taguchi ◽  
Hisaya Hasegawa ◽  
Mika Ishige ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
High Risk ◽  
Rare Diseases ◽  
Pediatric Patients ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background The prophylactic use of anti-respiratory syncytial virus (RSV) antibody (palivizumab) for severe RSV infection is not approved in Japan in specified groups of infants with neuromuscular diseases or other rare diseases associated with reduced ventilation competence or difficulty in expectoration, which increase the risk of exacerbation of severe RSV infection. The objective of this study is to investigate the efficacy, safety, and pharmacokinetics of palivizumab in pediatric patients with those rare diseases for which palivizumab is not indicated at present. Methods/design This study is a multicenter, uncontrolled, open-label study planned to be carried out between July 1, 2019 and June 30, 2022 at 7 medical institutions in Japan. The study population will be recruited from among neonates, infants, or children aged 24 months or younger with a condition falling under any of the following 5 disease groups: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. The planned sample size is 18 subjects, including at least 3 subjects per disease group. Throughout the RSV season, at least 4 continuous doses of palivizumab will be administered intramuscularly at 15 mg/kg at intervals of 30 days. The efficacy and safety of palivizumab will be comprehensively evaluated based on the incidence of RSV-related hospitalization, and serum palivizumab concentration, serum anti-palivizumab antibody concentration, and the occurrence of adverse events/reactions after the start of palivizumab treatment. Discussion This study will evaluate the efficacy and safety of palivizumab in pediatric patients with rare diseases which place them at high risk of severe RSV infection, but which fall outside the current indications for palivizumab prophylaxis. The generated data will have implications for the regulatory approval of prophylactic palivizumab treatment in this patient group. Trial registration This study has been prospectively registered in Japic Clinical Trials Information, which is managed and administered by the Japan Pharmaceutical Information Center (registration number: JapicCTI-194946, registration date: September 10, 2019).

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

scholarly journals Respiratory Syncytial Virus Immunoprophylaxis with Palivizumab: 12-Year Observational Study of Usage and Outcomes in Canada

2021 ◽  
Author(s):  
Ian Mitchell ◽  
Abby Li ◽  
Candice L. Bjornson ◽  
Krista L. Lanctot ◽  
Bosco A. Paes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Burden Of Illness ◽  
Respiratory Illness ◽  
Smoking Exposure ◽  
Key Points ◽  
Rsv Infection ◽  
History Of ◽  
Syncytial Virus ◽  
Airway Anomalies

Objective This study aimed to evaluate palivizumab (PVZ) use, trends in indications, and outcomes of respiratory illness hospitalizations (RIH) and respiratory syncytial virus hospitalizations (RSVH). Study Design It involves a large, Canadian prospective (2005–2017) observational multicenter study of children at high risk for RSV infection. Results A total of 25,003 infants (56.3% male) were enrolled at 32 sites; 109,579 PVZ injections were administered. Indications included: prematurity (63.3%); “miscellaneous” (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%). The “miscellaneous” group increased over time (4.4% in 2005–2006 to 22.5% in 2016–2017) and included: trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual “unclassified” group. Adherence measured by expected versus actual doses plus correct interdose interval was 64.7%. A total of 2,054 RIH occurred (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH 1.6%). Risk factors for RSVH included having siblings, attending daycare, family history of atopy, smoking exposure, and crowded household. Infants with 5 risk factors were 9.0 times (95% CI or confidence interval 4.4–18.2; p < 0.0005) more likely to have RSVH than infants without risk factors. Three adverse events occurred; none were fatal. Conclusion Results are relevant to both clinicians and decision-makers. We confirmed the safety of PVZ. Use of PVZ increased steadily for children with miscellaneous conditions and medical complexity. Medical and social factors pose a risk for severe RIH and RSVH with accompanying burden of illness. A vaccine that protects against RSV is urgently required. Key Points

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