scholarly journals Presumed Risk Factors and Biomarkers for Severe Respiratory Syncytial Virus Disease and Related Sequelae: Protocol for an Observational Multicenter, Case-Control Study From the Respiratory Syncytial Virus Consortium in Europe (RESCEU)

2020 ◽  
Vol 222 (Supplement_7) ◽  
pp. S658-S665 ◽  
Author(s):  
Kimberley Jefferies ◽  
Simon B Drysdale ◽  
Hannah Robinson ◽  
Elizabeth Ann Clutterbuck ◽  
Luke Blackwell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Disease Severity ◽  
Lower Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respiratory tract infection and hospitalization in children < 5 years of age worldwide. While there are known clinical risk factors for severe RSV infection, the majority of those hospitalized are previously healthy infants. There is consequently an unmet need to identify biomarkers that predict host response, disease severity, and sequelae. The primary objective is to identify biomarkers of severe RSV acute respiratory tract infection (ARTI) in infants. Secondary objectives include establishing biomarkers associated with respiratory sequelae following RSV infection and characterizing the viral load, RSV whole-genome sequencing, host immune response, and transcriptomic, proteomic, metabolomic and epigenetic signatures associated with RSV disease severity. Six hundred thirty infants will be recruited across 3 European countries: the Netherlands, Spain, and the United Kingdom. Participants will be recruited into 2 groups: (1) infants with confirmed RSV ARTI (includes upper and lower respiratory tract infections), 500 without and 50 with comorbidities; and (2) 80 healthy controls. At baseline, participants will have nasopharyngeal, blood, buccal, stool, and urine samples collected, plus complete a questionnaire and 14-day symptom diary. At convalescence (7 weeks ± 1 week post-ARTI), specimen collection will be repeated. Laboratory measures will be correlated with symptom severity scores to identify corresponding biomarkers of disease severity. Clinical Trials Registration NCT03756766.

Factors associated with severe respiratory syncytial virus disease in hospitalised children: a retrospective analysis

2021 ◽  
pp. archdischild-2021-322435
Author(s):  
Jeremy Anderson ◽  
Michelle Oeum ◽  
Eva Verkolf ◽  
Paul V Licciardi ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Severe Disease ◽  
Severe Respiratory Syncytial Virus ◽  
Factors Associated ◽  
Rsv Infection ◽  
Syncytial Virus

BackgroundEarly recognition of children at risk of severe respiratory syncytial virus (RSV) lower respiratory tract infection is important as it informs management decisions. We aimed to evaluate factors associated with severe disease among young children hospitalised with RSV infection.MethodsWe conducted a retrospective cohort study of all children <2 years of age hospitalised for RSV lower respiratory tract infection at a single tertiary paediatric hospital over three RSV seasons (January 2017–December 2019). We classified children as having ‘moderate’ or ‘severe’ disease based on the level of respiratory intervention and used univariable and multivariable regression models to determine factors associated with severe disease.ResultsOf 970 hospitalised children, 386 (40%) were classified as having ‘severe’ and 584 (60%) as having ‘moderate’ RSV disease. On multivariable analyses, age <2 months (OR: 2.3, 95% CI 1.6 to 3.3, p<0.0001), prematurity (OR: 1.6, 95% CI 1.1 to 2.4, p=0.02) and RSV–parainfluenza virus type 3 (PIV3) codetection (OR: 2.6, 95% CI 1.05 to 6.5, p=0.04) were independently associated with severe disease.ConclusionYounger age, prematurity and PIV3 codetection were associated with severe RSV disease in children <2 years of age hospitalised with RSV infection. The association between PIV3 and severe RSV disease is a novel finding and warrants further investigation.

scholarly journals The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

2019 ◽  
Vol 55 (4) ◽  
pp. 224-235
Author(s):  
Lisa Avery ◽  
Charles Hoffmann ◽  
Karen M. Whalen
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Adverse Reactions ◽  
Immunocompromised Patients ◽  
Syncytial Virus

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain >10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy.

scholarly journals 2630. Treatment of RSV Lower Respiratory Tract Infection in Two Immunocompromised Children with Polyclonal Immunoglobulin Containing Standardized Levels of Neutralizing Anti-RSV Antibody

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S918-S918
Author(s):  
Emily Ruth Levy ◽  
Theresa Madigan ◽  
Matthew Binnicker ◽  
jimmy mond ◽  
W Charles Huskins
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Nasal Congestion ◽  
Cell Transplant ◽  
Transplant Patients ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRTI) in immunocompromised children. There is no standard effective treatment, though ribavirin (inhaled or oral), pooled human intravenous immunoglobulin (IVIG), and monoclonal anti-RSV antibody (palivizumab) have been described. RI-002 (ADMA Biologics Inc.) is a pooled human polyclonal IVIG that contains standardized levels of neutralizing anti-RSV antibodies. It was recently FDA-approved for prophylaxis in primary immunodeficiency patients and has been used as compassionate treatment for RSV LRTI in stem cell transplant patients. Methods Two children with T-cell lymphoblastic lymphoma, both undergoing delayed intensification chemotherapy, were diagnosed with RSV LRTI. They were both treated with RI-002 under an emergency FDA Investigational New Drug protocol. Results Patient 1, a 4-year-old boy, was admitted with fever, neutropenia and nasal congestion, and diagnosed with RSV infection on hospital day (HD) 5. On HD17, he was intubated for respiratory failure. IVIG, palivizumab, and daily oral ribavirin were administered. On HD18, he required high frequency oscillator ventilation, nitric oxide, and paralysis. He was given RI-002 (1.5 g/kg on HD20 and 0.75 g/kg on HD22). He was placed on veno-venous extracorporeal membrane oxygenation (ECMO) on HD23. RSV PCR crossing point (Cp) values trended higher, but remained positive (table). On HD33, RI-002 was re-dosed (0.75 g/kg). Pulmonary compliance and chest CTs improved (figure). On HD52, ECMO support was discontinued. He was discharged on HD88, and currently requires no respiratory support. Patient 2, a 5-year-old boy, was admitted with fever, neutropenia, nasal congestion, cough, and stridor and diagnosed with RSV infection (HD1). He required nasal cannula oxygen. IVIG and daily oral ribavirin were administered. He was given RI-002 (1.5 g/kg on HD3 and 0.75 g/kg on HD5). By HD5, he was afebrile; oxygen was discontinued. He was discharged HD6. Conclusion Human polyclonal IVIG containing standardized levels of neutralizing anti-RSV antibodies may be useful in the treatment of RSV LRTI in immunocompromised children. Future studies on the role of RI-002 in treatment of RSV infection in immunocompromised children are warranted. Disclosures All authors: No reported disclosures.

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