Inpatient burden of respiratory syncytial virus (RSV) in Switzerland, 2003 to 2021: an analysis of administrative data.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalisations in infants (age < 1 year) and young children. Little is known on RSV epidemiology and related inpatient healthcare resource use (HCRU) in Switzerland.AimTo explore RSV-related hospitalisations, inpatient HCRU and medical costs in all age groups, and risk factors for infant hospitalisations in Switzerland.MethodsWe used national hospital registry data from 2003 to 2021 identifying RSV cases with ICD-10-GM codes, and described demographic characteristics, HCRU and associated medical costs of RSV inpatients. The effect of risk factors on infant hospitalisation was estimated with logistic regression.ResultsWe observed a general increase and biannual pattern in RSV hospitalisations between 2003/04 and 2018/19, with 3,575 hospitalisations in 2018/19 and 2,487 in 2019/20 before numbers declined in 2020/21 (n = 902). Around two thirds of all hospitalisations occurred in infants. Mean (median) age was 118 (85) days in hospitalised infants and 74 (77) years in hospitalised adult patients (> 18 years); 7.2% of cases required intensive care unit stay. Mean inpatient medical costs were estimated at EUR 8,046. Most (90.8%) hospitalised infants with RSV were born after 35 weeks of gestation without bronchopulmonary dysplasia or congenital heart disease. Low birth weight, gestational age and congenital disorders were associated with a higher risk for hospitalisation.ConclusionsRSV leads to a substantial number of hospitalisations and peaks in hospital capacity utilisation. Measures to protect all infants from an RSV hospitalisation are essential in addressing this public health challenge.

Burden of Respiratory Syncytial Virus (RSV) Infection Among Adults in Nursing and Care Homes: A Systematic Review.

BACKGROUND: Older adults in nursing and care homes (NCHs) are vulnerable to severe respiratory syncytial virus (RSV) infection, hospitalization, and death. This study aimed to gather data on RSV disease among older adults in NCHs and identify reported risk factors for RSV hospitalization and case fatality. METHODS: The study protocol was registered in PROSPERO (CRD42022371908). We searched MEDLINE, EMBASE, and Global Health databases to identify articles published between 2000 and 2023. Observational and experimental studies conducted among older adults in NCHs requiring assistive care and reporting RSV illness were included and relevant data were extracted. RESULTS: Of 18,690 studies screened, 32 were selected for full-text review, and 20 were included. Overall, the number of NCH residents ranged from 42 to 1459 with a mean age between 67.6 and 85 years. Attack rates ranged from 6.7% to 47.6% and annual incidence ranged from 0.5% to 14%. Case fatality rates ranged from 7.7% to 23.1%. We found similar annual incidence rates of RSV-positive acute respiratory infection (ARI) of 4582 (95% CI: 3259-6264) and 4785 (95% CI: 2258-10,141) per 100,000 reported in two studies. Annual incidence rate of RSV-positive lower respiratory tract infection was 3040 (95% CI: 1986-4454) cases per 100,000 adults. Annual RSV-ARI hospital admission rates were between 600 (95% CI: 190-10,000) and 1104 (95% CI: 350-1930) per 100,000 person-years. Among all RSV disease cases, commonly reported chronic medical conditions included chronic obstructive pulmonary disease (COPD), heart failure, ischemic heart disease, coronary artery disease, hypertension, diabetes, kidney dysfunction, cerebrovascular accident, malignancies, dementia, and those with a Charlson comorbidity score > 6.5. CONCLUSION: Data on RSV infection among NCH residents are limited and largely heterogeneous but document a high risk of illness, frequent hospitalization, and high mortality. Preventive interventions, such as vaccination, should be considered for this high-risk population. Nationally representative epidemiologic studies and NCH-based viral pathogen surveillance could more precisely assess the burden on NCH residents.

Circulation of new lineages of RSV-A and RSV-B in Kuwait shows high diversity in the N- and O-linked glycosylation sites in the G protein between 2020 and 2022.

The human respiratory syncytial virus (RSV) is a significant health concern, particularly for infants, young children, and the elderly. This virus is known to evolve continuously due to environmental factors and herd immunity. In light of this, our study aimed to analyze the genetic variability of the G protein in RSV-A and RSV-B genotypes in Kuwait from 2020 to 2022. Between January 2020 and September 2022, we collected 490 respiratory samples from hospitalized patients with acute respiratory tract infections. These samples were tested and confirmed positive for RSV using multiplex Real-Time PCR. Subsequently, the samples underwent nucleic acid sequencing using the advanced Nanopore sequencing technology to analyze the full-length G gene. Sequence analysis showed that 64 isolates (76%) were RSV-A, and 20 isolates (24%) were RSV-B. The G genes of RSV-A belonged to genotype GA2.3.5, while all the RSV-B genotypes belonged to GB5.0.5a. New lineages and sub-lineages of RSV-A and RSV-B were detected, indicating the circulation of new strains in Kuwait. Many unique and new amino acid changes, including insertions, were found in the G proteins of Kuwaiti isolates, with the highest variability in the second hypervariable region. An increased number of N and O-linked glycosylation sites were also identified in the G protein, which could speculate to alter the antigenicity of RSV. The identified changes in the G protein of RSV-A and RSV-B genotypes might result from immune pressure and could affect the antigenic characteristics of circulating strains in Kuwait. This could potentially lead to new RSV variants that can evade the immune response. Our in-depth analysis of the G proteins of both RSV-A and RSV-B could aid in the development of more potent treatments and vaccines.

Analysis of the epidemic characteristics of common respiratory pathogens infection in children in a 3A special hospital.

OBJECTIVE: To analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection. METHODS: A retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity. RESULTS: From December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p < 0.05); Among children in different age groups, the older the age, the older the Flu A The higher the infection rate of MP (p < 0.05), the higher the positive rate of RSV in children with younger age (p < 0.05). The positive rate of ADV in children aged 3-6 years and > 6 years was higher than that in children aged 0-3 years (p < 0.05); Flu A and MP are popular throughout the year, and the positive rate peaks during the period of temperature rise and air quality decline from February to March, and during the period of temperature drop and air quality index rise from August to November, The positive rate of RSV peaked after the turning point of temperature rise from March to April. The infection rate was higher during the period of sharp decline in air quality from March to May and sharp decline in temperature in November, The positive rate of ADV was higher at the turning point of temperature rise from February to March, and then the infection rate decreased. During the period of sharp temperature drop from August to November, the positive rate increased sharply, and the peak of infection occurred; As the disease worsens, The positive rates of Flu A, Flu B, RSV, MP and combined infection with more than two pathogens were all increased (p < 0.05). CONCLUSION: After the new coronavirus epidemic in 2022, Flu A and MP have the highest infection rate of respiratory pathogens in children, showing a peak growth in general, with epidemic characteristics changing with environmental temperature, air quality and seasons. The main disease type is upper respiratory tract infection, MP and adv infections were mainly in male children, Flu A, MP and ADV infections are more common in older children, RSV infection was more common in younger children; Flu A, Flu B, RSV and MP infection and the co infection of more than two pathogens may more easily lead to the occurrence of severe pneumonia.

Genomic characterization of human respiratory syncytial virus circulating in Islamabad, Pakistan, during an outbreak in 2022-2023.

In this study, conducted at the National Institute of Health, Islamabad, during an outbreak of human respiratory syncytial virus (hRSV) from December 2022 to January 2023, the first whole-genome sequences of hRSV isolates from Islamabad, Pakistan, were determined. Out of 10 positive samples, five were sequenced, revealing the presence of two genotypes: RSV-A (GA2.3.5, ON1 strain) and RSV-B (GB5.0.5.a, BA-10 strain). A rare non-synonymous substitution (E232G) in G the protein and N276S in the F protein were found in RSV-A. In RSV-B, the unique mutations K191R, Q209R, and I206M were found in the F protein. These mutations could potentially influence vaccine efficacy and viral pathogenicity. This research underscores the importance of genomic surveillance for understanding RSV diversity and guiding public health responses in Pakistan.

Evaluation of Three Multiplex Real-time Reverse Transcription PCR Assays for Simultaneous Detection of SARS-CoV-2, Influenza A/B, and Respiratory Syncytial Virus in Nasopharyngeal Swabs.

BACKGROUND: In the coronavirus disease 2019 (COVID-19) pandemic era, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (Flu), and respiratory syncytial virus (RSV) is important in the rapid differential diagnosis in patients with respiratory symptoms. Three multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assays have been recently developed commercially in Korea: PowerChek™ SARS-CoV-2, Influenza A&B Multiplex Real-time PCR Kit (PowerChek; KogeneBiotech); STANDARD™ M Flu/SARS-CoV-2 Real-time Detection Kit (STANDARD M; SD BioSensor); and Allplex™ SARS-CoV-2/FluA/FluB/RSV Assay (Allplex; Seegene). We evaluated the analytical and clinical performances of these kits. METHODS: A limit of detection tests were performed and cross-reactivity analysis was executed using clinical respiratory samples. Ninety-seven SARS-CoV-2-positive, 201 SARS-CoV-2-negative, 71 influenza A-positive, 50 influenza B-positive, 78 RSV-positive, and 207 other respiratory virus-positive nasopharyngeal swabs were tested using the three assays. The AdvanSure™ respiratory viruses rRT-PCR assay (AdvanSure; LG Life Sciences) was used as a comparator assay for RSV. RESULTS: Except in influenza B, in SARS-CoV-2 and influenza A, there were no significant differences in detecting specific genes of the viruses among the three assays. All three kits did not cross-react with common respiratory viruses. All three kits had greater than 92% positive percent agreement and negative percent agreement and ≥ 0.95 kappa value in the detection of SARS-CoV-2 and flu A/B. Allplex detected RSV more sensitively than AdvanSure. CONCLUSION: The overall performance of three multiplex rRT-PCR assays for the concurrent detection of SARS-CoV-2, influenza A/B, and RSV was comparable. These kits will promote prompt differential diagnosis of COVID-19, influenza, and RSV infection in the COVID-19 pandemic era.

Exploring the epidemiological changes of common respiratory viruses since the COVID-19 pandemic: a hospital study in Hangzhou, China.

Adenovirus, respiratory syncytial virus, and influenza virus are common causes of respiratory infections. The COVID-19 pandemic had a significant impact on their prevalence. The aim of this study was to analyze the epidemic changes of common respiratory viruses in the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China, from October of 2017 to February of 2021. We collected statistics from 121,529 patients in the outpatient and inpatient departments of the hospital who had throat or nose swabs collected for testing for four virus antigens by the colloidal gold method. Of these, 13,200 (10.86%) were positive for influenza A virus, 8,402 (6.91%) were positive for influenza B virus, 6,056 (4.98%) were positive for adenovirus, and 4,739 (3.90%) were positive for respiratory syncytial virus. The positivity rates of the influenza A virus (0-14 years old, P = 0.376; over 14 years old, P = 0.197) and respiratory syncytial virus (0-14 years old, P = 0.763; over 14 years old, P = 0.465) did not differ significantly by gender. After January of 2020, influenza virus infection decreased significantly. The positivity rate of respiratory syncytial virus remained high, and its epidemic season was similar to before. Strict respiratory protection and regulation of crowd activities have a great impact on the epidemic characteristics of viruses. After major changes in the public health environment, virus epidemics and their mutations should be monitored closely, extensively, and continuously.

Potent Human Single-Domain Antibodies Specific for a Novel Prefusion Epitope of Respiratory Syncytial Virus F Glycoprotein.

Respiratory syncytial virus (RSV) poses great health threats to humans. However, there are no licensed vaccines or therapeutic drugs to date. Only one humanized monoclonal antibody, palivizumab, is available on the market, but it is used prophylactically and is limited to infants with high risk. With advances in antibody engineering, it has been found that a single-domain antibody (sdAb) can be therapeutically administered by inhalation, which would be more efficient for respiratory diseases. Here, we identified two human sdAbs, m17 and m35, by phage display technology. They specifically bind to RSV fusion glycoprotein (F protein) in the prefusion state with subnanomolar affinity and potently neutralize both RSV subtypes A and B with 50% inhibitory concentration (IC50) values ranging from pM to nM. Interestingly, these sdAbs recognize a novel epitope, termed VI, that is unique to the prefusion state. This epitope is located at the C terminus of the F1 subunit, close to the viral membrane, and might be sterically restricted. We further find that m17 and m35 neutralize RSV by preventing the prefusion F conformational arrangement, thus inhibiting membrane fusion. These two sdAbs have the potential to be further developed as therapeutic candidates and may also provide novel insight for developing other antiviral reagents against RSV. IMPORTANCE Because respiratory syncytial virus (RSV) can cause serious respiratory disease in immunodeficient groups, including infants and seniors, the development of vaccines and therapeutic drugs, such as neutralizing antibodies, is urgently needed. Compared to the conventional full-length antibody, a single-domain antibody (sdAb) has been demonstrated to be efficient for respiratory diseases when administered by inhalation, thereby potentially introducing a kind of novel therapeutic agent in the market. Here, we discovered two potent neutralizing human sdAbs against RSV that recognized a novel prefusion epitope, termed VI, and prevented conformational arrangement during the fusion process. Our work provides not only therapeutic candidates but also novel targets for new drug and vaccine development.

Severity of RSV infection in Southern European elderly patients during two consecutive winter seasons (2017-2018).

In Europe, the respiratory syncytial virus (RSV) surveillance system is very heterogeneous and there is growing evidence of the importance of RSV infections resulting in hospitalization of elderly patients. The aim of this study was to assess the severity of RSV infection in the elderly living in the aged Southern European countries. We conducted a retrospective study of elderly patients ( ≥65-year old) admitted for laboratory-confirmed RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons (2017-2018). Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on radiologically confirmed pneumonia, use of noninvasive ventilation (NIV), and in-hospital death (IHD). A total of 166 elderly patients were included. Pneumonia was evident in 29.5%. NIV was implemented in 16.3%, length of stay was 11.8 ± 12.2 days, and IHD occurred in 12.1%. Multivariable analyses revealed that the risk of pneumonia was higher in patients with chronic kidney disease (CKD) (odds ratio [OR]: 2.57; 95% confidence interval [CI]: 1.12-5.91); the use of NIV was higher in patients with obstructive sleep apnea or obesity hypoventilation syndrome (OSA or OHS) (OR: 5.38; 95% CI: 1.67-17.35) and CKD (OR: 2.52; 95% CI: 1.01-6.23); the risk of IHD was higher in males (OR: 3.30; 95% CI: 1.07-10.10) and in patients with solid neoplasm (OR: 9.06; 95% CI: 2.44-33.54) and OSA or OHS (OR: 8.39; 95% CI: 2.14-32.89). Knowledge of factors associated with RSV infection severity may aid clinicians to set priorities and reduce disease burden. Development of effective antiviral treatment and vaccine against RSV is highly desirable.

Respiratory syncytial virus B sequence analysis reveals a novel early genotype.

Respiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.

Respiratory Syncytial Virus G Protein Sequence Variability among Isolates from St. Petersburg, Russia, during the 2013-2014 Epidemic Season.

Human respiratory syncytial virus (RSV) is the most common cause of upper and lower respiratory tract infections in infants and young children. It is actively evolving under environmental and herd immunity influences. This work presents, for the first time, sequence variability analysis of RSV G gene and G protein using St. Petersburg (Russia) isolates. Viruses were isolated in a cell culture from the clinical samples of 61 children hospitalized (January-April 2014) with laboratory-confirmed RSV infection. Real-time RT-PCR data showed that 56 isolates (91.8%) belonged to RSV-A and 5 isolates (8.2%) belonged to RSV-B. The G genes were sequenced for 27 RSV-A isolates and all of them belonged to genotype ON1/GA2. Of these RSV-A, 77.8% belonged to the ON1(1.1) genetic sub-cluster, and 14.8% belonged to the ON1(1.2) sub-cluster. The ON1(1.3) sub-cluster constituted a minor group (3.7%). Many single-amino acid substitutions were identified in the G proteins of St. Petersburg isolates, compared with the Canadian ON1/GA2 reference virus (ON67-1210A). Most of the amino acid replacements were found in immunodominant B- and T-cell antigenic determinants of G protein. These may affect the antigenic characteristics of RSV and influence the host antiviral immune response to currently circulating viruses.

Genetic Diversity and Molecular Epidemiology of Circulating Respiratory Syncytial Virus in Central Taiwan, 2008-2017.

In this study, we investigated the molecular evolution and phylodynamics of respiratory syncytial virus (RSV) over 10 consecutive seasons (2008-2017) and the genetic variability of the RSV genotypes ON1 and BA in central Taiwan. The ectodomain region of the G gene was sequenced for genotyping. The nucleotide and deduced amino acid sequences of the second hypervariable region of the G protein in RSV ON1 and BA were analyzed. A total of 132 RSV-A and 81 RSV-B isolates were obtained. Phylogenetic analysis revealed that the NA1, ON1, and BA9 genotypes were responsible for the RSV epidemics in central Taiwan in the study period. For RSV-A, the NA1 genotype predominated during the 2008-2011 seasons. The ON1 genotype was first detected in 2011 and replaced NA1 after 2012. For RSV-B, the BA9 and BA10 genotypes cocirculated from 2008 to 2010, but the BA9 genotype has predominated since 2012. Amino acid sequence alignments revealed the continuous evolution of the G gene in the ectodomain region. The predicted N-glycosylation sites were relatively conserved in the ON1 (site 237 and 318) and BA9 (site 296 and 310) genotype strains. Our results contribute to the understanding and prediction of the temporal evolution of RSV at the local level.

Characteristics of human metapneumovirus infection in adults hospitalized for community-acquired influenza-like illness in France, 2012-2018: a retrospective observational study.

OBJECTIVES: To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). METHODS: This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset <7 days). Data were collected from five French teaching hospitals over six consecutive winters (2012-2018). Respiratory viruses were identified by multiplex reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. hMPV + patients were compared with hMPV- patients, influenza+ and respiratory syncytial virus (RSV)+ patients using multivariate logistic regressions. Primary outcome was the prevalence of hMPV in patients hospitalized for ILI. RESULTS: Among the 3148 patients included (1449 (46%) women, 1988 (63%) aged 65 and over; 2508 (80%) with chronic disease), at least one respiratory virus was detected in 1604 (51%, 95% confidence interval (CI) 49-53), including 100 cases of hMPV (100/3148, 3% 95% CI 3-4), of which 10 (10%) were viral co-infection. In the hMPV + patients, mean length of stay was 7 days, 62% (56/90) developed a complication, 21% (14/68) were admitted to intensive care unit and 4% (4/90) died during hospitalization. In comparison with influenza + patients, hMPV + patients were more frequently >65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. CONCLUSIONS: Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.

High prevalence of SARS-CoV-2 and influenza A virus (H1N1) coinfection in dead patients in Northeastern Iran.

In the last months of 2019, an outbreak of fatal respiratory disease started in Wuhan, China, and quickly spread to other parts of the world. It was named COVID-19, and to date, thousands of cases of infection and death are reported worldwide. This disease is associated with a wide range of symptoms, which makes accurate diagnosis of it difficult. During previous severe acute respiratory syndrome (SARS) pandemic in 2003, researchers found that the patients with fever, cough, or sore throat had a 5% influenza virus-positive rate. This finding made us think that the wide range of symptoms and also relatively high prevalence of death in our patients may be due to the coinfection with other viruses. Thus, we evaluated the coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with other respiratory viruses in dead patients in North Khorasan. We evaluated the presence of influenza A/B virus, human metapneumovirus, bocavirus, adenovirus, respiratory syncytial virus (RSV), and parainfluenza viruses in 105 SARS-CoV-2 positive dead patients, using polymerase chain reaction (PCR) and reverse transcription PCR tests. We found coinfection with influenza virus in 22.3%, RSV, and bocavirus in 9.7%, parainfluenza viruses in 3.9%, human metapneumovirus in 2.9%, and finally adenovirus in 1.9% of SARS-CoV-2 positive dead cases. Our findings highlight a high prevalence of coinfection with influenza A virus and the monopoly of coinfection with Human metapneumovirus in children.

Systematic review and meta-analysis of the prevalence of common respiratory viruses in children < 2 years with bronchiolitis in the pre-COVID-19 pandemic era.

INTRODUCTION: The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in bronchiolitis. This systematic review and meta-analysis was initiated to clarify the prevalence of respiratory viruses in children with bronchiolitis in the pre-COVID-19 pandemic era. METHODS: We performed an electronic search through Pubmed and Global Index Medicus databases. We included observational studies reporting the detection rate of common respiratory viruses in children with bronchiolitis using molecular assays. Data was extracted and the quality of the included articles was assessed. We conducted sensitivity, subgroups, publication bias, and heterogeneity analyses using a random effect model. RESULTS: The final meta-analysis included 51 studies. Human respiratory syncytial virus (HRSV) was largely the most commonly detected virus 59.2%; 95% CI [54.7; 63.6]). The second predominant virus was Rhinovirus (RV) 19.3%; 95% CI [16.7; 22.0]) followed by Human bocavirus (HBoV) 8.2%; 95% CI [5.7; 11.2]). Other reported viruses included Human Adenovirus (HAdV) 6.1%; 95% CI [4.4; 8.0]), Human Metapneumovirus (HMPV) 5.4%; 95% CI [4.4; 6.4]), Human Parainfluenzavirus (HPIV) 5.4%; 95% CI [3.8; 7.3]), Influenza 3.2%; 95% CI [2.2; 4.3], Human Coronavirus (HCoV) 2.9%; 95% CI [2.0; 4.0]), and Enterovirus (EV) 2.9%; 95% CI [1.6; 4.5]). HRSV was the predominant virus involved in multiple detection and most codetections were HRSV + RV 7.1%, 95% CI [4.6; 9.9]) and HRSV + HBoV 4.5%, 95% CI [2.4; 7.3]). CONCLUSIONS: The present study has shown that HRSV is the main cause of bronchiolitis in children, we also have Rhinovirus, and Bocavirus which also play a significant role. Data on the role played by SARS-CoV-2 in children with acute bronchiolitis is needed. REVIEW REGISTRATION: PROSPERO, CRD42018116067.

Clinical impact of respiratory virus in pulmonary exacerbations of children with Cystic Fibrosis.

BACKGROUNDS: Cystic Fibrosis (CF) is a genetic, multisystemic, progressive illness that causes chronic suppurative lung disease. A major cause of morbimortality in this condition are pulmonary exacerbations. Although classically attributed to bacterial infections, respiratory virus have been increasingly recognized in its ethiopathogeny. METHODS: Nasopharyngeal swab samples were collected from children < 18 years old with CF in Rio de Janeiro, Brazil, with pulmonary exacerbation criteria. Samples were submitted to RT-PCR for Adenovirus, Influenza A and B, Parainfluenza Virus, Respiratory Syncytial Virus (RSV), Metapneumovirus and Rhinovirus. Virus positive and virus negative groups were compared in regards to clinical presentation, severity of exacerbation and bacterial colonization. RESULTS: Out of 70 samples collected from 48 patients, 35.7% were positive for respiratory viruses. Rhinovirus were the most common (28% of all positive samples), followed by RSV. The virus positive group was associated with change in sinus discharge (p = 0.03). Considering only patients younger than five years old, positive virus detection was also associated with fever (p = 0.01). There was no significant difference in clinical severity or in bacterial colonization between virus positive and negative groups. CONCLUSIONS: Prospective studies are still needed to assess the long term impact of viral infections in patients with CF, and their interaction with the bacterial microbiome in these patients.

A Respiratory Syncytial Virus Attachment Gene Variant Associated with More Severe Disease in Infants Decreases Fusion Protein Expression, Which May Facilitate Immune Evasion.

This study identified a genotype of respiratory syncytial virus (RSV) associated with increased acute respiratory disease severity in a cohort of previously healthy term infants. The genotype (2stop+A4G) consists of two components. The A4G component is a prevalent point mutation in the 4th position of the gene end transcription termination signal of the G gene of currently circulating RSV strains. The 2stop component is two tandem stop codons at the G gene terminus, preceding the gene end transcription termination signal. To investigate the biological role of these RSV G gene mutations, recombinant RSV strains harboring either a wild-type A2 strain G gene (one stop codon preceding a wild-type gene end signal), an A4G gene end signal preceded by one stop codon, or the 2stop+A4G virulence-associated combination were generated and characterized. Infection with the recombinant A4G (rA4G) RSV mutant resulted in transcriptional readthrough and lower G and fusion (F) protein levels than for the wild type. Addition of a second stop codon preceding the A4G point mutation (2stop+A4G) restored G protein expression but retained lower F protein levels. These data suggest that RSV G and F glycoprotein expression is regulated by transcriptional and translational readthrough. Notably, while rA4G and r2stop+A4G RSV were attenuated in cells and in naive BALB/c mice compared to that for wild-type RSV, the r2stop+A4G RSV was better able to infect BALB/c mice in the presence of preexisting immunity than rA4G RSV. Together, these factors may contribute to the maintenance and virulence of the 2stop+A4G genotype in currently circulating RSV-A strains.IMPORTANCE Strain-specific differences in respiratory syncytial virus (RSV) isolates are associated with differential pathogenesis in mice. However, the role of RSV genotypes in human infection is incompletely understood. This work demonstrates that one such genotype, 2stop+A4G, present in the RSV attachment (G) gene terminus is associated with greater infant disease severity. The genotype consists of two tandem stop codons preceding an A-to-G point mutation in the 4th position of the G gene end transcription termination signal. Virologically, the 2stop+A4G RSV genotype results in reduced levels of the RSV fusion (F) glycoprotein. A recombinant 2stop+A4G RSV was better able to establish infection in the presence of existing RSV immunity than a virus harboring the common A4G mutation. These data suggest that regulation of G and F expression has implications for virulence and, potentially, immune evasion.

Epidemiology and clinical characteristics of viral infections in hospitalized children and adolescents with cancer in Lebanon.

BACKGROUND: Viral infections in children and adolescents with malignancy are commonly encountered and have a significant impact on morbidity and mortality. Studies and epidemiological data regarding viral infections in children with cancer in developing countries are lacking. This retrospective cohort study aims to assess the burden of viral infections in children and adolescents with cancer, by assessing prevalence, risk factors, as well as morbidity and mortality of common viruses over a period of 8 years. METHODS AND FINDINGS: Medical records of cancer patients treated at the Children Cancer Center of Lebanon were reviewed and 155 participants under the age of 21 were identified with at least one documented viral infection during the period from July 2009 to November 2017. This subset included 136 participants with active malignancy and 19 participants with a history of cancer who underwent hematopoietic stem cell transplantation [HSCT] and were in remission; the latter group was analyzed separately. Information regarding participant characteristics, hospital course, and complications were obtained. Associations between viral infections and certain factors were assessed. In the cohort, 64% were male, 81% were Lebanese. In participants with active malignancy, 90% received chemotherapy in the 6 months preceding the viral infection episode, 11% received radiotherapy. 51% of participants were neutropenic at the time of viral detection, and 77% were lymphopenic. 17% experienced a bacterial co-infection, and 3 experienced a viral co-infection. Among 162 viral infection episodes, clinically diagnosed skin infections, mainly herpes simplex virus type 1 and varicella-zoster virus, were the most common [44% of cases]. These were followed by laboratory-proven systemic herpes infections: cytomegalovirus [14%] and Epstein-Barr virus [6%]. Respiratory viruses: influenza and respiratory syncytial virus, accounted for 9% and 4%, respectively, whereas rotavirus represented 11% and BK virus represented 3% of cases. Acute lymphocytic leukemia was the most prevalent neoplasia [57%]. Fever was the most common presenting symptom [55%] and febrile neutropenia was the reason for admission in 24% of cases. The mean length of stay was significantly longer in participants with cytomegalovirus infections and significantly lower in rotavirus infection. Admission to the ICU occurred in 9%, complications in 8%, and mortality in 5%. Participants with viral infections post-HSCT were noted to have a significantly longer length of hospital stay compared to non-HSCT participants, with no other significant differences in clinical course and outcome. The study was limited by its retrospective nature and by the late introduction and underuse of multiplex PCR panels, which may have led to underdiagnosis of viral infections. CONCLUSIONS: Viral infections were prevalent in our sample of cancer patients and may have contributed to morbidity and mortality. Newly available viral diagnostics are likely to vastly increase the number and scope of detectable viral infections in this population. Prospective studies using multiplex PCR technology with systematic testing of patients will be more helpful in defining the burden of viral infections. Furthermore, efforts at antimicrobial stewardship would benefit from the identification of viral causes of infection and limit the unnecessary use of antibiotics in the pediatric cancer population.

Inside the lungs of COVID-19 disease.

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease.