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Viruses Jul 2023Nosocomial pneumonia (NP) represents a leading cause of morbidity and mortality in hospitalized patients. Historically, clinicians have considered hospital-acquired... (Review)
Review
Nosocomial pneumonia (NP) represents a leading cause of morbidity and mortality in hospitalized patients. Historically, clinicians have considered hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), which comprise NP, to be essentially bacterial processes. As such, patients suspected of having either HAP or VAP are initially treated with broad-spectrum antibiotics, and few clinicians search for a possible culprit virus. Recent reports which build on earlier studies, however, indicate that viruses likely play an important role in NP. Studies employing viral diagnostics as part of the evaluation for NP indicate that common respiratory viruses can spread nosocomially and lead to HAP and VAP. Similarly, studies of the general epidemiology of respiratory viral infections, such as influenza, respiratory syncytial virus, adenovirus, and rhinovirus, confirm that these pathogens are important causes of NP, especially among immunosuppressed and pediatric patients. More importantly, these more contemporary analyses reveal that one cannot, based on clinical characteristics, distinguish a viral from a bacterial cause of NP. Additionally, viral HAP and VAP result in crude mortality rates that rival or exceed those reported in bacterial NP. Rigorous prospective, multicenter trials are needed to confirm the significance of respiratory viruses in NP, as are studies of novel therapeutics for these viral infections.
Topics: Humans; Child; Cross Infection; Prospective Studies; Healthcare-Associated Pneumonia; Adenoviridae; Respiratory Syncytial Virus, Human
PubMed: 37632017
DOI: 10.3390/v15081676 -
Current Opinion in Infectious Diseases Oct 2023To describe the current global burden of respiratory syncytial virus (RSV) in infants and its implications for morbidity, health resources and economic costs. (Review)
Review
PURPOSE OF REVIEW
To describe the current global burden of respiratory syncytial virus (RSV) in infants and its implications for morbidity, health resources and economic costs.
RECENT FINDINGS
New prophylactic therapies are on the horizon for RSV in the form of long-acting monoclonal antibodies suitable for healthy infants and maternal immunizations.
SUMMARY
Despite being responsible for significant global infant morbidity and mortality, until recently there have been no effective therapeutics available for healthy infants to protect them from RSV. Several new drugs are likely to be available within the next few years which could help relieve a huge burden on healthcare systems over the coming winters.
Topics: Infant; Humans; Respiratory Syncytial Viruses; Cost of Illness; Antibodies, Monoclonal; Health Resources; Immunization
PubMed: 37610444
DOI: 10.1097/QCO.0000000000000952 -
Viruses Mar 2020Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include... (Review)
Review
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies.
Topics: Animals; Antiviral Agents; Binding Sites; Drug Discovery; Humans; Models, Molecular; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Protein Binding; Structure-Activity Relationship; Virus Internalization
PubMed: 32245118
DOI: 10.3390/v12030342 -
Frontiers in Immunology 2022Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal... (Review)
Review
Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, the current concept of pregnancy as a state of systemic immunosuppression seems oversimplified and outdated. Undoubtedly, in pregnancy the maternal immune system undergoes complex changes to establish and maintain tolerance to the fetus while still protecting from pathogens. In addition to downregulated maternal immunity, hormonal changes, and mechanical adaptation (e.g., restricted lung expansion) make the pregnant woman more susceptible to respiratory pathogens, such as influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Depending on the infectious agent and timing of the infection during gestation, fetal pathology can range from mild to severe, and even fatal. Influenza is associated with a higher risk of morbidity and mortality in pregnant women than in the general population, and, especially during the third trimester of pregnancy, mothers are at increased risk of hospitalization for acute cardiopulmonary illness, while their babies show higher risk of complications such as prematurity, respiratory and neurological illness, congenital anomalies, and admission to neonatal intensive care. RSV exposure is associated with selective immune deficit, remodeling of cholinergic innervation in the developing respiratory tract, and abnormal airway smooth muscle contractility, which may predispose to postnatal airway inflammation and hyperreactivity, as well as development of chronic airway dysfunction in childhood. Although there is still limited evidence supporting the occurrence of vertical transmission of SARS-CoV-2, the high prevalence of prematurity among pregnant women infected by SARS-CoV-2 suggests this virus may alter immune responses at the maternal-fetal interface, affecting both the mother and her fetus. This review aims at summarizing the current evidence about the short- and long-term consequences of intrauterine exposure to influenza, RSV, and SARS-CoV-2 in terms of neonatal and pediatric outcomes.
Topics: COVID-19; Child; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Respiratory Syncytial Viruses; SARS-CoV-2
PubMed: 35359954
DOI: 10.3389/fimmu.2022.853009 -
Frontiers in Immunology 2022Correlates of protection are key for vaccine development against any pathogen. In this paper we summarize recent information about correlates for vaccines against...
Correlates of protection are key for vaccine development against any pathogen. In this paper we summarize recent information about correlates for vaccines against dengue, Ebola, influenza, pneumococcal, respiratory syncytial virus, rotavirus, shigella, tuberculosis and Zika virus.
Topics: Humans; Influenza Vaccines; Respiratory Syncytial Virus, Human; Influenza, Human; Zika Virus; Zika Virus Infection
PubMed: 36776392
DOI: 10.3389/fimmu.2022.1081107 -
BMC Infectious Diseases Jun 2020Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being...
BACKGROUND
Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age.
METHODS
The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies.
DISCUSSION
The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.
Topics: Antibodies, Monoclonal; Antiviral Agents; Child, Preschool; Drug Resistance, Bacterial; Female; Genome, Viral; Genotype; Humans; Immunization, Passive; Infant; Infant, Newborn; Male; Molecular Epidemiology; Polymorphism, Genetic; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 32591017
DOI: 10.1186/s12879-020-05175-4 -
Viruses Dec 2020The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant... (Review)
Review
The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.
Topics: Animals; Biomarkers; Gene Expression Regulation, Viral; Host Specificity; Host-Pathogen Interactions; Humans; Immunity, Innate; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Viral Tropism; Virus Replication
PubMed: 33276587
DOI: 10.3390/v12121381 -
Influenza and Other Respiratory Viruses May 2023Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of RSV-related disease burden, and to provide evidence to help establish a surveillance system.
METHODS
We searched the English- and Chinese-language databases for articles published between January 1, 2010 and June 2, 2022. The quality of the included articles was assessed using the Agency for Healthcare Research and Quality scale. Random-effects models were used for data synthesis and subgroup analyses. This review was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022372972).
RESULTS
We included 44 studies (149,321,171 participants), all of which were of medium or high quality. The pooled RSV-related disease incidence, hospitalization rate, in-hospital mortality, and overall mortality rates in children aged 5 years and younger were 9.0 per 100 children per year (95% confidence interval [CI]: 7.0-11.0), 1.7 per 100 children per year (95% CI: 1.3-2.1), 0.5 per 100 children per year (95% CI: 0.4-0.5), and 0.05 per 100 children per year (95% CI: 0.04-0.06), respectively. Age, economics, surveillance types, case definition, and data source were all recognized as influencing factors.
CONCLUSIONS
A standardized and unified RSV surveillance system is required. Case definition and surveillance types should be fully considered for surveillance of different age groups.
Topics: United States; Child; Humans; Child, Preschool; Incidence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Hospitalization
PubMed: 37223668
DOI: 10.1111/irv.13145 -
Signal Transduction and Targeted Therapy Aug 2023Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in...
Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in infants and the elderly, yet no effective vaccine or antiviral therapy is available. The RSV genome encodes the nucleoprotein (N) that forms helical assembly to encapsulate and protect the RNA genome from degradation, and to serve as a template for transcription and replication. Previous crystal structure revealed a decameric ring architecture of N in complex with the cellular RNA (N-RNA) of 70 nucleotides (70-nt), whereas cryo-ET reconstruction revealed a low-resolution left-handed filament, in which the crystal monomer structure was docked with the helical symmetry applied to simulate a nucleocapsid-like assembly of RSV. However, the molecular details of RSV nucleocapsid assembly remain unknown, which continue to limit our complete understanding of the critical interactions involved in the nucleocapsid and antiviral development that may target this essential process during the viral life cycle. Here we resolve the near-atomic cryo-EM structure of RSV N-RNA that represents roughly one turn of the helical assembly that unveils critical interaction interfaces of RSV nucleocapsid and may facilitate development of RSV antiviral therapy.
Topics: Aged; Infant; Humans; Respiratory Syncytial Viruses; Cryoelectron Microscopy; Nucleocapsid; Antiviral Agents; RNA
PubMed: 37607909
DOI: 10.1038/s41392-023-01602-5 -
Revista Espanola de Quimioterapia :... Jun 2024The properties of the main surface proteins and the viral cycle of the respiratory syncytial virus (RSV) make it an attractive pathogen from the perspective of... (Review)
Review
The properties of the main surface proteins and the viral cycle of the respiratory syncytial virus (RSV) make it an attractive pathogen from the perspective of microbiology. The virus gets its name from the manner it infects cells, which enables it to produce syncytia, which allow the virus' genetic material to move across cells without having to release viral offspring to the cellular exterior, reducing immune system identification. This causes a disease with a high impact in both children and adults over 60, which has sparked the development of several preventive interventions based on vaccines and monoclonal antibodies for both age groups. The epidemiological characteristics of this virus, which circulates in epidemics throughout the coldest months of the year and exhibits a marked genetic and antigenic drift due to its high mutation capability, must be taken into consideration while using these preventive methods. The most important microbiological and epidemiological elements of RSV are covered in this study, along with how they have affected the creation of preventive medications and their use in the future.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Vaccines
PubMed: 38515332
DOI: 10.37201/req/006.2024