Healthcare resource use and economic burden attributable to respiratory syncytial virus in the United States: a claims database analysis

Amand, Caroline; Tong, Sabine; Kieffer, Alexia; Kyaw, Moe H.

doi:10.1186/s12913-018-3066-1

Cited by 66 publications

(52 citation statements)

References 36 publications

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“…estimated 14,000 deaths per year in the United States (2). Hospitalization due to RSV is a major economic burden, especially in preterm infants and older adults (3).…”

mentioning

confidence: 99%

Conformational Flexibility in Respiratory Syncytial Virus G Neutralizing Epitopes

Fedechkin

George

Castrejon

et al. 2020

J Virol

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Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in infants and the elderly. Currently, no vaccine or effective treatment exists for RSV. The RSV G glycoprotein mediates viral attachment to cells and contributes to pathogenesis by modulating host immunity through interactions with the human chemokine receptor CX3CR1. Antibodies targeting the RSV G central conserved domain are protective in both prophylactic and postinfection animal models. Here, we describe the crystal structure of the broadly neutralizing human monoclonal antibody 3G12 bound to the RSV G central conserved domain. Antibody 3G12 binds to a conformational epitope composed of highly conserved residues, explaining its broad neutralization activity. Surprisingly, RSV G complexed with 3G12 adopts a distinct conformation not observed in previously described RSV G-antibody structures. Comparison to other structures reveals that the RSV G central conserved domain is flexible and can adopt multiple conformations in the regions flanking the cysteine noose. We also show that restriction of RSV G flexibility with a proline mutation abolishes binding to antibody 3G12 but not antibody 3D3, which recognizes a different conformation of RSV G. Our studies provide new insights for rational vaccine design, indicating the importance of preserving both the global structural integrity of antigens and local conformational flexibility at antigenic sites, which may elicit a more diverse antibody response and broader protection against infection and disease. IMPORTANCE Respiratory syncytial virus (RSV) causes severe respiratory infections in infants, young children, and the elderly, and currently, no licensed vaccine exists. In this study, we describe the crystal structure of the RSV surface glycoprotein G in complex with a broadly neutralizing human monoclonal antibody. The antibody binds to RSV G at a highly conserved region stabilized by two disulfide bonds, but it captures RSV G in a conformation not previously observed, revealing that this region is both structured and flexible. Importantly, our findings provide insight for the design of vaccines that elicit diverse antibodies, which may provide broad protection from infection and disease. KEYWORDS X-ray crystallography, broadly neutralizing antibodies, protein structurefunction, respiratory syncytial virus R espiratory syncytial virus (RSV) is a globally prevalent virus that affects the airways and lungs. Infants and young children are at the highest risk of severe outcomes from RSV infection, with 33.1 million episodes of lower respiratory tract infection and approximately 3.2 million hospital visits and 118,200 deaths per year worldwide in children under the age of 5 years due to RSV (1). RSV is also a major cause of illness in adults older than 65 years of age and immunocompromised individuals, with an

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“…estimated 14,000 deaths per year in the United States (2). Hospitalization due to RSV is a major economic burden, especially in preterm infants and older adults (3).…”

mentioning

confidence: 99%

Conformational Flexibility in Respiratory Syncytial Virus G Neutralizing Epitopes

Fedechkin

George

Castrejon

et al. 2020

J Virol

View full text Add to dashboard Cite

show abstract

“…They found that higher annual costs in the RSV infants compared to the matched controls across all age groups; ranging from $7,535 to $40,405. 22 None of the well-appearing infants < 60 days of age with no sick contacts and respiratory symptoms tested positive for RSV. Although, RSV causes significant cost to healthcare, cost may be decreased by not testing this population for RSV/flu.…”

Section: Discussionmentioning

confidence: 94%

Febrile infants without respiratory symptoms or sick contacts: Are chest radiographs or RSV/influenza testing indicated?

Ozcan

Laskowski

Sahai

et al. 2020

Preprint

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Objectives: Serious bacterial infection rates in febrile infants <60 days are about 8-11%. Less than 1% of febrile infants with no respiratory symptoms will have pneumonia however, chest radiography (CXR) rates remain between 30-60%. Rapid Respiratory Syncytial Virus (RSV) and influenza (flu) testing is common, however, there is not enough data to determine if febrile infants without any respiratory symptoms should be tested. The goal of this study is to determine the rate of positive CXR and RSV/flu results in febrile infants with no respiratory symptoms and no sick contacts. Methods: Well-appearing febrile infants between 7-60 days of age who presented to the pediatric emergency department (PED) from September 1 st , 2015 through October 30 th , 2017 were enrolled. Demographic data, respiratory symptoms, CXR findings and RSV/flu results were collected. SAS statistical software was used for analysis. Results: 129 infants met enrollment criteria. Of the 129 infants, 58 (45.0%) had no respiratory symptoms and no sick contacts. Of these 58, 36 (62%) received a CXR and none of them had any abnormal findings, 48 (83%) had RSV/flu testing, no patients tested positive for RSV and only one patient tested positive for flu. Costs of CXR and RSV/flu testing for this cohort was $19,788. Conclusion: The absence of positive CXRs in this patient population reinforces the current recommendations that CXR is not indicated. The low incidence of RSV/flu indicate that routine testing may not be necessary in this population especially outside of the flu season. Reduced testing could decrease overall costs to the healthcare system as well as radiation exposure to this population.

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“…They found that higher annual costs in the RSV infants compared to the matched controls across all age groups; ranging from $7,535 to $40,405. 22 None of the well-appearing infants < 60 days of age with no sick contacts and respiratory symptoms tested positive for RSV. Although, RSV causes signi cant cost to healthcare, cost may be decreased by not testing this population for RSV/ u.…”

Section: Discussionmentioning

confidence: 94%

Febrile infants without respiratory symptoms or sick contacts: Are chest radiographs or RSV/influenza testing indicated?

Ozcan

Laskowski

Sahai

et al. 2020

Preprint

View full text Add to dashboard Cite

Objectives: Serious bacterial infection rates in febrile infants <60 days are about 8-11%. Less than 1% of febrile infants with no respiratory symptoms will have pneumonia however, chest radiography (CXR) rates remain between 30-60%. Rapid Respiratory Syncytial Virus (RSV) and influenza (flu) testing is common, however, there is not enough data to determine if febrile infants without any respiratory symptoms should be tested. The goal of this study is to determine the rate of positive CXR and RSV/flu results in febrile infants with no respiratory symptoms and no sick contacts. Methods: Well-appearing febrile infants between 7-60 days of age who presented to the pediatric emergency department (PED) from September 1st, 2015 through October 30th, 2017 were enrolled. Demographic data, respiratory symptoms, CXR findings and RSV/flu results were collected. SAS statistical software was used for analysis. Results: 129 infants met enrollment criteria. Of the 129 infants, 58 (45.0%) had no respiratory symptoms and no sick contacts. Of these 58, 36 (62.1%) received a CXR and none of them had any abnormal findings, 48 (82.8%) had RSV/flu testing, no patients tested positive for RSV and only one patient tested positive for flu. Costs of CXR and RSV/flu testing for this cohort was $19,788. Conclusion: The absence of positive CXRs in this patient population reinforces the current recommendations that CXR is not indicated. The low incidence of RSV/flu indicate that routine testing may not be necessary in this population especially outside of the flu season. Reduced testing could decrease overall costs to the healthcare system as well as radiation exposure to this population.

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Healthcare resource use and economic burden attributable to respiratory syncytial virus in the United States: a claims database analysis

Cited by 66 publications

References 36 publications

Conformational Flexibility in Respiratory Syncytial Virus G Neutralizing Epitopes

Conformational Flexibility in Respiratory Syncytial Virus G Neutralizing Epitopes

Febrile infants without respiratory symptoms or sick contacts: Are chest radiographs or RSV/influenza testing indicated?

Febrile infants without respiratory symptoms or sick contacts: Are chest radiographs or RSV/influenza testing indicated?

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