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BMC Medicine Jun 2023Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested... (Meta-Analysis)
Meta-Analysis
Understanding the age spectrum of respiratory syncytial virus associated hospitalisation and mortality burden based on statistical modelling methods: a systematic analysis.
BACKGROUND
Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested for RSV. We aimed to understand the full age spectrum of RSV morbidity and mortality burden based on statistical modelling studies, as well as the value of modelling studies in RSV disease burden estimation.
METHODS
The databases Medline, Embase and Global Health were searched to identify studies published between January 1, 1995, and December 31, 2021, reporting RSV-associated excess hospitalisation or mortality rates of any case definitions using a modelling approach. All reported rates were summarised using median, IQR (Interquartile range) and range by age group, outcome and country income group; where applicable, a random-effects meta-analysis was conducted to combine the reported rates. We further estimated the proportion of RSV hospitalisations that could be captured in clinical databases.
RESULTS
A total of 32 studies were included, with 26 studies from high-income countries. RSV-associated hospitalisation and mortality rates both showed a U-shape age pattern. Lowest and highest RSV acute respiratory infection (ARI) hospitalisation rates were found in 5-17 years (median: 1.6/100,000 population, IQR: 1.3-18.5) and < 1 year (2235.7/100,000 population, 1779.1-3552.5), respectively. Lowest and highest RSV mortality rates were found in 18-49 years (0.1/100,000 population, 0.06-0.2) and ≥ 75 years (80.0/100,000 population, 70.0-90.0) for high-income countries, respectively, and in 18-49 years (0.3/100,000 population, 0.1-2.4) and < 1 year (143.4/100,000 population, 143.4-143.4) for upper-middle income countries. More than 70% of RSV hospitalisations in children < 5 years could be captured in clinical databases whereas less than 10% of RSV hospitalisations could be captured in adults, especially for adults ≥ 50 years. Using pneumonia and influenza (P&I) mortality could potentially capture half of all RSV mortality in older adults but only 10-30% of RSV mortality in children.
CONCLUSIONS
Our study provides insights into the age spectrum of RSV hospitalisation and mortality. RSV disease burden using laboratory records alone could be substantially severely underreported for age groups ≥ 5 years. Our findings confirm infants and older adults should be prioritised for RSV immunisation programmes.
TRIAL REGISTRATION
PROSPERO CRD42020173430.
Topics: Infant; Child; Humans; Aged; Child, Preschool; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Models, Statistical; Influenza, Human; Hospitalization
PubMed: 37365569
DOI: 10.1186/s12916-023-02932-5 -
Viruses May 2021RNA synthesis in respiratory syncytial virus (RSV), a negative-sense (-) nonsegmented RNA virus, consists of viral gene transcription and genome replication. Gene... (Review)
Review
RNA synthesis in respiratory syncytial virus (RSV), a negative-sense (-) nonsegmented RNA virus, consists of viral gene transcription and genome replication. Gene transcription includes the positive-sense (+) viral mRNA synthesis, 5'-RNA capping and methylation, and 3' end polyadenylation. Genome replication includes (+) RNA antigenome and (-) RNA genome synthesis. RSV executes the viral RNA synthesis using an RNA synthesis ribonucleoprotein (RNP) complex, comprising four proteins, the nucleoprotein (N), the large protein (L), the phosphoprotein (P), and the M2-1 protein. We provide an overview of the RSV RNA synthesis and the structural insights into the RSV gene transcription and genome replication process. We propose a model of how the essential four proteins coordinate their activities in different RNA synthesis processes.
Topics: Animals; Genome, Viral; Humans; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Ribonucleoproteins; Viral Proteins
PubMed: 34063087
DOI: 10.3390/v13050834 -
Microbiology Spectrum Aug 2023Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses...
Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses at the population level is still very limited. We here conducted a prospective laboratory-based etiological study by enrolling 14,426 patients suffered from acute respiratory infection (ARI) in Beijing, China during 2005 to 2015. All 18 respiratory viruses were simultaneously tested for each nasal and throat swabs collected from enrolled patients using molecular tests. The virus correlations were quantitatively evaluated, and the respiratory viruses could be divided into two panels according to the positive and negative correlations. One included influenza viruses (IFVs) A, B, and respiratory syncytial virus (RSV), while the other included human parainfluenza viruses (HPIVs) 1/3, 2/4, adenovirus (Adv), human metapneumovirus (hMPV), and enterovirus (including rhinovirus, named picoRNA), α and β human coronaviruses (HCoVs). The viruses were positive-correlated in each panel, while negative-correlated between panels. After adjusting the confounding factors by vector autoregressive model, positive interaction between IFV-A and RSV and negative interaction between IFV-A and picoRNA are still be observed. The asynchronous interference of IFV-A significantly delayed the peak of β human coronaviruses epidemic. The binary property of the respiratory virus interactions provides new insights into the viral epidemic dynamics in human population, facilitating the development of infectious disease control and prevention strategies. Systematic quantitative assessment of the interactions between different respiratory viruses is pivotal for the prevention of infectious diseases and the development of vaccine strategies. Our data showed stable interactions among respiratory viruses at human population level, which are season irrelevant. Respiratory viruses could be divided into two panels according to their positive and negative correlations. One included influenza virus and respiratory syncytial virus, while the other included other common respiratory viruses. It showed negative correlations between the two panels. The asynchronous interference between influenza virus and β human coronaviruses significantly delayed the peak of β human coronaviruses epidemic. The binary property of the viruses indicated transient immunity induced by one kind of virus would play role on subsequent infection, which provides important data for the development of epidemic surveillance strategies.
Topics: Humans; Infant; Prospective Studies; Viruses; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Orthomyxoviridae
PubMed: 37378522
DOI: 10.1128/spectrum.00019-23 -
Viruses Jul 2021Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children <5 years of age worldwide and repeated infections throughout... (Review)
Review
Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children <5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design.
Topics: Animals; Antibodies, Viral; GTP-Binding Proteins; Humans; Mice; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Viral Proteins
PubMed: 34372490
DOI: 10.3390/v13071214 -
Clinical and Experimental Immunology Dec 2023Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of... (Review)
Review
Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine strategies, a clear view of the immunological background and differences between various target populations is of crucial importance. In this study, we have assessed both quantitative and qualitative aspects of RSV-specific serum antibodies, including IgG/IgA levels, IgG subclasses, antibody-dependent complement deposition, cellular phagocytosis, and NK cell activation (ADNKA). Samples were collected cross-sectionally in different age groups (11-, 24-, and 46-month-old children, adults, and older adults; n = 31-35 per group) and longitudinally following natural RSV infection in (older) adults (2-36 months post-infection; n = 10). We found that serum of 24-month-old children induces significantly lower ADNKA than the serum of adults (P < 0.01), which is not explained by antibody levels. Furthermore, in (older) adults we observed boosting of antibody levels and functionality at 2-3 months after RSV infection, except for ADNKA. The strongest decrease was subsequently observed within the first 9 months, after which levels remained relatively stable up to three years post-infection. Together, these data provide a comprehensive overview of the functional landscape of RSV-specific serum antibodies in the human population, highlighting that while antibodies reach adult levels already at a young age, ADNKA requires more time to fully develop.
Topics: Infant; Child; Humans; Aged; Child, Preschool; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Antibodies, Viral; Immunoglobulin G; Antibodies, Neutralizing
PubMed: 37605554
DOI: 10.1093/cei/uxad101 -
Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01 -
Viruses May 2021Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza viruses (HPIVs) are leading causes of respiratory disease in young... (Review)
Review
Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza viruses (HPIVs) are leading causes of respiratory disease in young children, the elderly, and individuals of all ages with immunosuppression. Vaccination strategies against these pneumoviruses and paramyxoviruses are vast in number, yet no licensed vaccines are available. Here, we review development of Sendai virus (SeV), a versatile pediatric vaccine that can (a) serve as a Jennerian vaccine against HPIV1, (b) serve as a recombinant vaccine against HRSV, HPIV2, HPIV3, and HMPV, (c) accommodate foreign genes for viral glycoproteins in multiple intergenic positions, (d) induce durable, mucosal, B-cell, and T-cell immune responses without enhanced immunopathology, (e) protect cotton rats, African green monkeys, and chimpanzees from infection, and (f) be formulated into a vaccine cocktail. Clinical phase I safety trials of SeV have been completed in adults and 3-6-year-old children. Clinical testing of SeVRSV, an HRSV fusion (F) glycoprotein gene recombinant, has also been completed in adults. Positive results from these studies, and collaborative efforts with the National Institutes of Health and the Serum Institute of India assist advanced development of SeV-based vaccines. Prospects are now good for vaccine successes in infants and consequent protection against serious viral disease.
Topics: Animals; Antibodies, Viral; Clinical Trials as Topic; Genetic Vectors; Mice; Parainfluenza Virus 1, Human; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Sendai virus; Vaccines, Synthetic; Viral Envelope Proteins; Viral Vaccines; Viruses
PubMed: 34072332
DOI: 10.3390/v13061023 -
Current Opinion in Infectious Diseases Apr 2024To highlight the respiratory syncytial virus (RSV) disease burden and the current developments and challenges in RSV prevention for older adults ≥60 years through... (Review)
Review
PURPOSE OF REVIEW
To highlight the respiratory syncytial virus (RSV) disease burden and the current developments and challenges in RSV prevention for older adults ≥60 years through analysis of RSV epidemiology and the effectiveness of emerging vaccines.
RECENT FINDINGS
In industrialized countries, RSV incidence rates and hospitalization rates among older adults are estimated to be 600.7 cases per 100 000 person-years and 157 hospitalizations per 100 000 person-years, respectively. Yet, accurately determining RSV morbidity and mortality in older adults is challenging, thus resulting in substantially under-estimating the disease burden. The in-hospital fatality rates vary substantially with age and geographies, and can be as high as 9.1% in developing countries. Two promising RSV vaccines for the elderly have been approved, demonstrating efficacies of up to 94.1%, signifying considerable advancement in RSV prevention. However, concerns over potential side effects remain.
SUMMARY
RSV is associated with a significant burden in older adults. While the landscape of RSV prevention in older adults is promising with the licensure of vaccines from two companies, current trial data underscore the need for additional studies. Addressing the real-world effectiveness of these vaccines, understanding potential rare side effects, and ensuring broad inclusivity in future trials are crucial steps to maximize their potential benefits.
Topics: Humans; Infant; Aged; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization; Cost of Illness; Vaccines
PubMed: 38197402
DOI: 10.1097/QCO.0000000000001000 -
Cellular and Molecular Life Sciences :... Feb 2024The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed... (Review)
Review
The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.
Topics: Animals; Humans; COVID-19; Pandemics; Complement System Proteins; Influenza, Human; Respiratory Syncytial Virus, Human
PubMed: 38368584
DOI: 10.1007/s00018-024-05157-8 -
Expert Review of Vaccines 2023Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young... (Review)
Review
INTRODUCTION
Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young children aged <2 years and the elderly are at particular risk of severe infections requiring hospitalization.
AREAS COVERED
This narrative review summarizes the epidemiology of RSV infection in Korea, with a particular focus on infants and the elderly, where possible, and highlights the need for effective vaccinations against RSV. Relevant papers were identified from a search of PubMed up to December 2021.
EXPERT OPINION
RSV infection is associated with a significant burden of illness in infants and the elderly worldwide and accounts for a substantial number of hospital admissions due to severe lower respiratory tract infections in both of these age groups in Korea. Vaccination has the potential to reduce the burden of acute RSV-associated disease and long-term consequences such as asthma. Increased understanding of the immune response to RSV, including mucosal immunity, and the innate and adaptive immune responses is needed. Technological advances in vaccine platforms could provide better approaches for achieving a safe and effective vaccine-induced immune response.
Topics: Infant; Aged; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Immunization; Vaccination; Respiratory Syncytial Viruses; Respiratory Tract Infections; Immunity, Mucosal; Republic of Korea; Respiratory Syncytial Virus, Human
PubMed: 36960592
DOI: 10.1080/14760584.2023.2189459