-
Infectious Disease Reports Mar 2024Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence... (Review)
Review
Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options.
PubMed: 38667752
DOI: 10.3390/idr16020026 -
Frontiers in Microbiology 2024Our study undertakes a detailed exploration of gene expression dynamics within human lung organ tissue equivalents (OTEs) in response to Influenza A virus (IAV), Human...
INTRODUCTION
Our study undertakes a detailed exploration of gene expression dynamics within human lung organ tissue equivalents (OTEs) in response to Influenza A virus (IAV), Human metapneumovirus (MPV), and Parainfluenza virus type 3 (PIV3) infections. Through the analysis of RNA-Seq data from 19,671 genes, we aim to identify differentially expressed genes under various infection conditions, elucidating the complexities of virus-host interactions.
METHODS
We employ Generalized Linear Models (GLMs) with Quasi-Likelihood (QL) F-tests (GLMQL) and introduce the novel Magnitude-Altitude Score (MAS) and Relaxed Magnitude-Altitude Score (RMAS) algorithms to navigate the intricate landscape of RNA-Seq data. This approach facilitates the precise identification of potential biomarkers, highlighting the host's reliance on innate immune mechanisms. Our comprehensive methodological framework includes RNA extraction, library preparation, sequencing, and Gene Ontology (GO) enrichment analysis to interpret the biological significance of our findings.
RESULTS
The differential expression analysis unveils significant changes in gene expression triggered by IAV, MPV, and PIV3 infections. The MAS and RMAS algorithms enable focused identification of biomarkers, revealing a consistent activation of interferon-stimulated genes (e.g., IFIT1, IFIT2, IFIT3, OAS1) across all viruses. Our GO analysis provides deep insights into the host's defense mechanisms and viral strategies exploiting host cellular functions. Notably, changes in cellular structures, such as cilium assembly and mitochondrial ribosome assembly, indicate a strategic shift in cellular priorities. The precision of our methodology is validated by a 92% mean accuracy in classifying respiratory virus infections using multinomial logistic regression, demonstrating the superior efficacy of our approach over traditional methods.
DISCUSSION
This study highlights the intricate interplay between viral infections and host gene expression, underscoring the need for targeted therapeutic interventions. The stability and reliability of the MAS/RMAS ranking method, even under stringent statistical corrections, and the critical importance of adequate sample size for biomarker reliability are significant findings. Our comprehensive analysis not only advances our understanding of the host's response to viral infections but also sets a new benchmark for the identification of biomarkers, paving the way for the development of effective diagnostic and therapeutic strategies.
PubMed: 38655085
DOI: 10.3389/fmicb.2024.1342328 -
BMC Infectious Diseases Apr 2024Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the...
BACKGROUND
Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020.
METHODS
Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records.
RESULTS
The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups.
DISCUSSION
In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.
Topics: Humans; China; Retrospective Studies; Respiratory Tract Infections; Male; Female; Middle Aged; Adult; Aged; Adolescent; Young Adult; Child; Child, Preschool; Acute Disease; Infant; Aged, 80 and over; Viruses; Hospitalization
PubMed: 38649799
DOI: 10.1186/s12879-024-09297-x -
Vaccine May 2024Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.
Topics: Animals; Antibodies, Neutralizing; Mice; Metapneumovirus; Vaccines, Virus-Like Particle; Female; Viral Fusion Proteins; Antibodies, Viral; Mice, Inbred BALB C; gag Gene Products, Human Immunodeficiency Virus; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine; Humans; Respiratory Syncytial Virus Vaccines; Recombinant Fusion Proteins; Respiratory Syncytial Virus Infections; Viral Vaccines
PubMed: 38641492
DOI: 10.1016/j.vaccine.2024.04.048 -
International Journal of Infectious... Jul 2024The COVID-19 pandemic significantly changed respiratory viruses' epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study...
Global analysis of respiratory viral circulation and timing of epidemics in the pre-COVID-19 and COVID-19 pandemic eras, based on data from the Global Influenza Surveillance and Response System (GISRS).
OBJECTIVES
The COVID-19 pandemic significantly changed respiratory viruses' epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study investigates whether the circulation patterns of respiratory viruses have returned to pre-pandemic norms by comparing their peak timing and duration during the first three SARS-CoV-2 seasons to pre-pandemic times.
METHODS
Global Influenza Surveillance and Response System data from 194 countries (2014-2023) was analyzed for epidemic peak timing and duration, focusing on pre-pandemic and pandemic periods across both hemispheres and the intertropical belt. The analysis was restricted to countries meeting specific data thresholds to ensure robustness.
RESULTS
In 2022/2023, the northern hemisphere experienced earlier influenza and respiratory syncytial virus (RSV) peaks by 1.9 months (P <0.001). The duration of influenza epidemics increased by 2.2 weeks (P <0.001), with RSV showing a similar trend. The southern hemisphere's influenza peak shift was not significant (P = 0.437). Intertropical regions presented no substantial change in peak timing but experienced a significant reduction in the duration for human metapneumovirus and adenovirus (7.2 and 6.5 weeks shorter, respectively, P <0.001).
CONCLUSIONS
The pandemic altered the typical patterns of influenza and RSV, with earlier peaks in 2022 in temperate areas. These findings highlight the importance of robust surveillance data to inform public health strategies on evolving viral dynamics in the years to come.
Topics: Humans; COVID-19; Influenza, Human; SARS-CoV-2; Global Health; Pandemics; Respiratory Syncytial Virus Infections; Seasons; Epidemics
PubMed: 38636684
DOI: 10.1016/j.ijid.2024.107052 -
Infectious Diseases & Clinical... Dec 2023This study aimed to estimate research productivity and general characteristics of research in different regions of the world in the field of human metapneumovirus (hMPV).
OBJECTIVE
This study aimed to estimate research productivity and general characteristics of research in different regions of the world in the field of human metapneumovirus (hMPV).
MATERIALS AND METHODS
We used the Web of Science (WoS) electronic database to retrieve articles on "human metapneumovirus," published up to March 31, 2023. Parameters such as research productivity, the total number of publications, average citation counts of all articles, research productivity by top publishing countries and affiliated organizations, links between countries/organizations, and top keywords were assessed.
RESULTS
We found 826 articles in the WoS database. The first article on hMPV was published in 2002, and 2008 was the year that the most articles on hMPV were published, with 70 articles. The articles were cited 26,797 times (14,498 times without self-citations) and 32.25 times on average per article. Hirsch (H)-index was 80. The year 2008 also had the highest number of citations, with more than 1800. The United States was the most productive country, producing 295 documents (35.714%), one-third of all publications in this field worldwide. Canada (6.5%) and Japan (6.5%) followed the United States regarding total hMPV publications worldwide. The leading funding agencies for hMPV research were from the United States, Europe, China, and Japan.
CONCLUSION
Our findings imply that developed countries should assist developing countries in enhancing their research infrastructures.
PubMed: 38633850
DOI: 10.36519/idcm.2023.250 -
Influenza and Other Respiratory Viruses Apr 2024Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human...
Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO-Defined Fast-Breathing Pneumonia in Pakistan.
BACKGROUND
Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast-breathing pneumonia in Karachi, Pakistan.
METHODS
We performed a cross-sectional analysis of nasopharyngeal swabs from children aged 2-59 months with fast-breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast-breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors.
FINDINGS
Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co-infections in three samples (two RSV-hMPV and one influenza-hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02-3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32-4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23-4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35-4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53-7.93).
CONCLUSION
We observed a high nasopharyngeal viral carriage among children with WHO-defined fast-breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status are important clinical predictors for viral nonsevere community-acquired pneumonia.
Topics: Child; Child, Preschool; Humans; Infant; Cross-Sectional Studies; Fever; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Pakistan; Respiratory Syncytial Virus, Human; World Health Organization
PubMed: 38616564
DOI: 10.1111/irv.13285 -
Scientific Reports Apr 2024The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are...
The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are responsible for severe respiratory tract infections in infants, young children, elderly individuals, adults with chronic medical conditions, and immunocompromised patients. Despite their large impact on human health, vaccines for hRSV were only recently introduced, and only limited treatment options exist. Here we show that Ginkgolic acid (GA), a natural compound from the extract of Ginkgo biloba, with known antiviral properties for several viruses, efficiently inhibits these viruses' infectivity and spread in cultures in a dose-dependent manner. We demonstrate that the drug specifically affects the entry step during the early stages on the viruses' life cycle with no effect on post-entry and late stage events, including viral gene transcription, genome replication, assembly and particles release. We provide evidence that GA acts as an efficient antiviral for members of the Pneumoviridae family and has the potential to be used to treat acute infections.
Topics: Child; Adult; Infant; Humans; Child, Preschool; Aged; Paramyxoviridae Infections; Metapneumovirus; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Virus Diseases; Respiratory Syncytial Virus Infections; Antiviral Agents; Salicylates
PubMed: 38589437
DOI: 10.1038/s41598-024-58032-8 -
BMC Pediatrics Apr 2024Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is...
BACKGROUND
Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is related to infections which are not medically attended. The perspective on infections in the community setting is necessary to understand the effects of the pandemic on non-pharmaceutical interventions.
METHODS
In the unique prospective LoewenKIDS cohort study, we compared the true monthly incidence of self-reported acute respiratory infections (ARI) in about 350 participants (aged 3-4 years old) between October 2019 to March 2020 (pre-pandemic period) and October 2020 to March 2021 (pandemic period). Parents reported children's symptoms using a diary. Parents were asked to take a nasal swab of their child during all respiratory symptoms. We analysed 718 swabs using Multiplex PCR for 25 common respiratory viruses and bacteria.
RESULTS
During the pre-pandemic period, on average 44.6% (95% CI: 39.5-49.8%) of children acquired at least one ARI per month compared to 19.9% (95% CI: 11.1-28.7%) during the pandemic period (Incidence Rate Ratio = 0.47; 95% CI: 0.41-0.54). The detection of influenza virus decreased absolute by 96%, respiratory syncytial virus by 65%, metapneumovirus by 95%, parainfluenza virus by 100%, human enterovirus by 96% and human bocavirus by 70% when comparing the pre-pandemic to the pandemic period. However, rhinoviruses were nearly unaffected by NPI. Co-detection (detection of more than one virus in a single symptomatic swab) was common in the pre-pandemic period (222 of 390 samples with viral detection; 56.9%) and substantially less common during the pandemic period (46 of 216 samples; 21.3%).
CONCLUSION
Non-pharmaceutical interventions strongly reduced the incidence of all respiratory infections in preschool children but did not affect rhinovirus.
Topics: Humans; Child, Preschool; Infant; Cohort Studies; Prospective Studies; COVID-19; Respiratory Tract Infections; Metapneumovirus; Rhinovirus
PubMed: 38561704
DOI: 10.1186/s12887-024-04686-2 -
Public Health May 2024To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy.
OBJECTIVES
To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy.
STUDY DESIGN
Outbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza.
METHODS
An epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted.
RESULTS
The outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9-14 years, 84.6% in those aged 15-24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period.
CONCLUSIONS
The fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved.
Topics: Adult; Child; Humans; Influenza, Human; Influenza A virus; Influenza A Virus, H3N2 Subtype; Refugees; Phylogeny; Virus Diseases; Influenza Vaccines; Disease Outbreaks
PubMed: 38554473
DOI: 10.1016/j.puhe.2024.02.027