Respiratory Syncytial Virus Virus Research Articles

Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings.

BackgroundThe true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life.MethodsThis prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods.ResultsOf 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval [CI], 5.88–9.08), 5.50 (95% CI, 4.21–7.07), and 2.87 (95% CI, 2.18–3.70) cases/100 person-years in children aged 0–5, 6–11, and 12–23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0–5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0–2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs.ConclusionsA substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most. Clinical Trials Registration. NCT01995175.

Epidemiology of community-acquired pneumonia among hospitalised children in Indonesia: a multicentre, prospective study

ObjectiveTo identify aetiologies of childhood community-acquired pneumonia (CAP) based on a comprehensive diagnostic approach.Design‘Partnerships for Enhanced Engagement in Research-Pneumonia in Paediatrics (PEER-PePPeS)’ study was an observational prospective cohort study conducted...

Off-season RSV epidemics in Australia after easing of COVID-19 restrictions

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection with the most severe disease in the young and elderly. Non-pharmaceutical interventions and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated regions of the Australian continent, New South Wales (NSW) and Australian Capital Territory (ACT) in the east, and Western Australia. Through genomic sequencing we reveal a major reduction in RSV genetic diversity following COVID-19 emergence with two genetically distinct RSV-A clades circulating cryptically, likely localised for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria and to cause extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic, as mitigation measures may disrupt seasonal patterns, causing larger or more severe outbreaks.

Detailed Analyses of Molecular Interactions between Favipiravir and RNA Viruses In Silico.

There are currently no antiviral agents for human metapneumovirus (HMPV), respiratory syncytial virus (RSV), mumps virus (MuV), or measles virus (MeV). Favipiravir has been developed as an anti-influenza agent, and this agent may be effective against these viruses in vitro. However, the molecular mechanisms through which the agent affects virus replication remain to be fully elucidated. Thus, to clarify the detailed molecular interactions between favipiravir and the RNA-dependent RNA polymerase (RdRp) of HMPV, RSV, MuV, MeV, and influenza virus, we performed in silico studies using authentic bioinformatics technologies. As a result, we found that the active form of favipiravir (favipiravir ribofuranosyl-5′-triphosphate [F-RTP]) can bind to the RdRp active sites of HMPV, RSV, MuV, and MeV. The aspartic acid residue of RdRp active sites was involved in the interaction. Moreover, F-RTP was incorporated into the growing viral RNA chain in the presence of nucleotide triphosphate and magnesium ions. The results suggested that favipiravir shows two distinct mechanisms in various viruses: RdRp active site inhibition and/or genome replication inhibition.

154. Circulation of Rhinovirus/Enterovirus Respiratory Infections in Children During 2020-21 in the United States

BackgroundSharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. MethodsWe conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020–January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson’s chi-squared. Data are provisional.ResultsAmong 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 – January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020– January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 – January 2021ConclusionDuring 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation.Disclosures Jennifer E. Schuster, MD, Merck, Sharpe, and Dohme (Individual(s) Involved: Self): Grant/Research Support Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Claire Midgley, PhD, Nothing to disclose Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

Can laboratory evaluation differentiate between coronavirus disease-2019, influenza, and respiratory syncytial virus infections? A retrospective cohort study

AimTo identify clinical and laboratory parameters that can assist in the differential diagnosis of coronavirus disease 2019 (COVID-19), influenza, and respiratory syncytial virus (RSV) infections.MethodsIn this retrospective cohort study, we obtained basic demographics and laboratory data from all 685 hospitalized patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, or RSV from 2018 to 2020. A multiple logistic regression was employed to investigate the relationship between COVID-19 and laboratory parameters.ResultsSARS-CoV-2 patients were significantly younger than RSV (P = 0.001) and influenza virus (P = 0.022) patients. SARS-CoV-2 patients also displayed a significant male predominance over influenza virus patients (P = 0.047). They also had significantly lower white blood cell count (median 6.3 × 106 cells/μ) compared with influenza virus (P < 0.001) and RSV (P = 0.001) patients. Differences were also observed in other laboratory values but were insignificant in a multivariate analysis.ConclusionsMale sex, younger age, and low white blood cell count can assist in the diagnosis of COVID-19 over other viral infections. However, the differences between the groups were not substantial enough and would probably not suffice to distinguish between the viral illnesses in the emergency department.

In-hospital and midterm post-discharge complications of adults hospitalised with respiratory syncytial virus infection in France, 2017-2019: an observational study.

The purpose of this study was to describe the clinical characteristics and in-hospital and post-discharge outcomes of respiratory syncytial virus (RSV) infection among adults hospitalised with influenza-like illness (ILI) and compared against patients admitted for influenza. Adults hospitalised with ILI were prospectively included from five French university hospitals over two consecutive winter seasons (2017/2018 and 2018/2019). RSV and influenza virus were detected by multiplex reverse transcription PCR on nasopharyngeal swabs. RSV-positive patients were compared to RSV-negative and influenza-positive hospitalised patients. Poisson regression models were used to estimate the adjusted prevalence ratio (aPR) associated with in-hospital and post-discharge outcomes between RSV and influenza infections. The in-hospital outcome was a composite of the occurrence of at least one complication, length of stay ≥7 days, intensive care unit admission, use of mechanical ventilation and in-hospital death. Post-discharge outcome included 30- and 90-day all-cause mortality and 90-day readmission rates. Overall, 1428 hospitalised adults with ILI were included. RSV was detected in 8% (114 of 1428) and influenza virus in 31% (437 of 1428). Patients hospitalised with RSV were older than those with influenza (mean age 73.0 versus 68.8 years, p=0.015) with a higher frequency of chronic respiratory or cardiac disease (52% versus 39%, p=0.012, and 52% versus 41%, p=0.039, respectively) and longer hospitalisation duration (median stay 8 versus 6 days, p<0.001). Anti-influenza therapies were less prescribed among RSV patients than influenza patients (20% versus 66%, p<0.001). In-hospital composite outcome was poorer in RSV patients (aPR 1.5, 95% CI 1.1-2.1) than in those hospitalised with influenza. No difference was observed for the post-discharge composite outcome (aPR 1.1, 95% CI 0.8-1.6). RSV infection results in serious respiratory illness, with worse in-hospital outcomes than influenza and with similar midterm post-discharge outcomes.

Is the surge in respiratory syncytial virus related to the COVID-19 pandemic? a clinical-based review

Respiratory syncytial virus (RSV) has been around for many years. Symptoms of the virus includes: cough, runny nose, loss of appetite, and a possible ear infection. Often times, the patient presents with bronchiolitis, which eventually escalates to RSV. Children most commonly affected by RSV are between the ages of 0-2. In December 2019, the first case of SARS-CoV-2 was discovered in China. Normally, the RSV virus sparks around the winter months; however, throughout the COVID -19 pandemic, RSV was at its all-time low. When SARS-CoV-2 started to decline in early April 2021, there was a spike in the respiratory syncytial virus among children.

Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe—results from the PED-MERMAIDS multicentre case–control study

BackgroundBoth pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to...

Seasonality of distinct respiratory viruses in a tropical city: implications for prophylaxis

The frequency and seasonality of viruses in tropical regions are scarcely reported. We estimated the frequency of seven respiratory viruses and assessed seasonality of respiratory syncytial virus (RSV) and influenza viruses in a tropical city. Children (age≤18years) with acute respiratory infection were investigated in Salvador, Brazil, between July 2014 and June 2017. Respiratory viruses were searched by direct immunofluorescence and real-time polymerase chain reaction for detection of RSV, influenza A virus, influenza B virus, adenovirus (ADV) and parainfluenza viruses (PIV) 1, 2 and 3. Seasonal distribution was evaluated by Prais-Winsten regression. Due to similar distribution, influenza A and influenza B viruses were grouped to analyse seasonality. The study group comprised 387 cases whose median (IQR) age was 26.4 (10.5-50.1) months. Respiratory viruses were detected in 106 (27.4%) cases. RSV (n=76; 19.6%), influenza A virus (n=11; 2.8%), influenza B virus (n=7; 1.8%), ADV (n=5; 1.3%), PIV 1 (n=5; 1.3%), PIV 3 (n=3; 0.8%) and PIV 2 (n=1; 0.3%) were identified. Monthly count of RSV cases demonstrated seasonal distribution (b3=0.626; P=0.003). More than half (42/76 [55.3%]) of all RSV cases were detected from April to June. Monthly count of influenza cases also showed seasonal distribution (b3=-0.264; P=0.032). Influenza cases peaked from November to January with 44.4% (8/18) of all influenza cases. RSV was the most frequently detected virus. RSV and influenza viruses showed seasonal distribution. These data may be useful to plan the best time to carry out prophylaxis and to increase the number of hospital beds.

Prevalence of Respiratory Viral Infections in Children with Asthma in Kermanshah

Background: Asthma is a chronic inflammatory disorder of lung airways, affecting about 300 million people worldwide. Several risk factors are involved in asthma development, such as environmental allergens, genetic susceptibility, and respiratory viral infections. Viral infections induce NF-kB and inflammatory pathways that lead to the production of cytokines, chemokines, and inflammatory proteins and, finally, a reduction of lung volume and function. Objectives: The aim of this study was to evaluate viral infections’ prevalence in children with asthma from 2016 to 2017. Methods: One hundred throat swab samples were collected from asthmatic children. Extraction of RNA and cDNA synthesis were performed to recognize parainfluenza viruses, rhinoviruses, influenza viruses, and respiratory syncytial virus (RSV) using real-time PCR. Also, the associations of age, sex, and other studied factors with asthmatic attacks were evaluated. Results: In this study, 41 viruses were detected, including 21 cases of rhinoviruses (51.22%), 10 cases of parainfluenza (24.39%), seven cases of respiratory syncytial virus (17.07%), and three cases of the influenza virus (7.32%). Regarding seasonal incidence, the prevalence of the viruses was high in autumn and winter, and there was a significant relationship between seasonal incidence and gender. However, there were no statistically significant relationships between the prevalence of the viruses and age or gender. Conclusions: The most important viral causes of childhood asthma in this study were found to be rhinoviruses, followed by parainfluenza. The lowest prevalence was related to the RSV and influenza virus, which the two viruses also showed the lowest seasonal outbreaks. Therefore, it can be said that with an increase in the seasonal incidence of respiratory viruses, the effects of these viruses will be greater on asthma.

Molecular epidemiology of Respiratory Syncytial Virus in children in sub‐Saharan Africa

This study investigated the molecular epidemiology of respiratory syncytial virus (RSV) among febrile children with acute respiratory tract infection in Ghana, Gabon, Tanzania and Burkina Faso between 2014-2017 as well as the evolution and diversification of RSV strains from other sub-Saharan countries. Pharyngeal swabs were collected at four study sites (Agogo, Ghana: n=490; Lambaréné, Gabon: n=182; Mbeya, Tanzania: n=293; Nouna, Burkina Faso: n=115) and analysed for RSV and other respiratory viruses using rtPCR. For RSV positive samples, sequence analysis of the second hypervariable region of the G-gene was performed. A dataset of RSV strains from sub-Saharan Africa (2011-2017) currently available in GenBank was compiled. Phylogenetic analysis was conducted to identify the diversity of circulating RSV genotypes. In total, 46 samples tested RSV positive (Ghana n=31 (6.3%), Gabon n=4 (2.2%), Tanzania n=9 (3.1%), Burkina Faso n=2 (1.7%)). The most common RSV co-infection was with rhinovirus. All RSV-A strains clustered with genotype ON1 strains with a 72-nucleotide duplication and all RSV-B strains belonged to genotype BAIX. Phylogenetic analysis of amino acid sequences from sub-Saharan Africa revealed the diversification into 11 different ON1 and 22 different BAIX lineages and differentiation of ON1 and BAIX strains into potential new sub-genotypes, provisionally named ON1-NGR, BAIX-KEN1, BAIX-KEN2 and BAIX-KEN3. The study contributes to an improved understanding of the molecular epidemiology of RSV infection in sub-Saharan Africa. It provides the first phylogenetic data for RSV from Tanzania, Gabon and Burkina Faso and combines it with RSV strains from all other sub-Saharan countries currently available in GenBank.

Incidence, risk factors, and viral etiology of community-acquired acute lower respiratory tract infection among older adults in rural north India.

BackgroundThere are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries.MethodsWe established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls.ResultsWe followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively.ConclusionIn this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

Molecular epidemiology of respiratory syncytial virus in children in sub-Saharan Africa.

This study investigated the molecular epidemiology of respiratory syncytial virus (RSV) among febrile children with acute respiratory tract infection in Ghana, Gabon, Tanzania and Burkina Faso between 2014 and 2017 as well as the evolution and diversification of RSV strains from other sub-Saharan countries. Pharyngeal swabs were collected at four study sites (Agogo, Ghana: n=490; Lambaréné, Gabon: n=182; Mbeya, Tanzania: n=293; Nouna, Burkina Faso: n=115) and analysed for RSV and other respiratory viruses using rtPCR. For RSV-positive samples, sequence analysis of the second hypervariable region of the G gene was performed. A dataset of RSV strains from sub-Saharan Africa (2011-2017) currently available in GenBank was compiled. Phylogenetic analysis was conducted to identify the diversity of circulating RSV genotypes. In total, 46 samples were tested RSV positive (Ghana n=31 (6.3%), Gabon n=4 (2.2%), Tanzania n=9 (3.1%) and Burkina Faso n=2 (1.7%)). The most common RSV co-infection was with rhinovirus. All RSV A strains clustered with genotype ON1 strains with a 72-nucleotide duplication and all RSV B strains belonged to genotype BAIX. Phylogenetic analysis of amino acid sequences from sub-Saharan Africa revealed the diversification into 11 different ON1 and 22 different BAIX lineages and differentiation of ON1 and BAIX strains into potential new sub-genotypes, provisionally named ON1-NGR, BAIX-KEN1, BAIX-KEN2 and BAIX-KEN3. The study contributes to an improved understanding of the molecular epidemiology of RSV infection in sub-Saharan Africa. It provides the first phylogenetic data for RSV from Tanzania, Gabon and Burkina Faso and combines it with RSV strains from all other sub-Saharan countries currently available in GenBank.

Seasonal association between viral causes of hospitalised acute lower respiratory infections and meteorological factors in China: a retrospective study

Acute lower respiratory infections (ALRIs) caused by respiratory viruses are common and persistent infectious diseases worldwide and in China, which have pronounced seasonal patterns. Meteorological factors have important roles in the seasonality of some major viruses, especially respiratory syncytial virus (RSV) and influenza virus. Our aim was to identify the dominant meteorological factors and to model their effects on common respiratory viruses in different regions of China. We analysed monthly virus data on patients hospitalised with ALRI from 81 sentinel hospitals in 22 provinces in mainland China from Jan 1, 2009, to Sept 30, 2013. We considered seven common respiratory viruses: RSV, influenza virus, human parainfluenza virus, adenovirus, human metapneumovirus, human bocavirus, and human coronavirus. Meteorological data of the same period were used to analyse relationships between virus seasonality and seven meteorological factors according to region (southern vs northern China). The geographical detector method was used to quantify the explanatory power of each meteorological factor, individually and interacting in pairs, on the respiratory viruses. 28 369 hospitalised patients with ALRI were tested, 10 387 (36·6%) of whom were positive for at least one virus, including RSV (4091 [32·0%] patients), influenza virus (2665 [20·8%]), human parainfluenza virus (2185 [17·1%]), adenovirus (1478 [11·6%]), human bocavirus (1120 [8·8%]), human coronavirus (637 [5·0%]), and human metapneumovirus (615 [4·8%]). RSV and influenza virus had annual peaks in the north and biannual peaks in the south. Human parainfluenza virus and human bocavirus had higher positive rates in the spring-summer months. Human metapneumovirus had an annual peak in winter-spring, especially in the north. Adenovirus and human coronavirus exhibited no clear annual seasonality. Temperature, atmospheric pressure, vapour pressure, and rainfall had most explanatory power on most respiratory viruses in each region. Relative humidity was only dominant in the north, but had no significant explanatory power for most viruses in the south. Hours of sunlight had significant explanatory power for RSV and influenza virus in the north, and for most viruses in the south. Wind speed was the only factor with significant explanatory power for human coronavirus in the south. For all viruses, interactions between any two of the paired factors resulted in enhanced explanatory power, either bivariately or non-linearly. Spatiotemporal heterogeneity was detected for most viruses in this study, and interactions between pairs of meteorological factors were found to enhance their influence on virus variation. These findings might be helpful to guide government planning, such as public health interventions, infection control practice, and timing of passive immunoprophylaxis, and might facilitate the development of future vaccine strategies. National Natural Science Foundation of China, the Ministry of Science and Technology of China, and the Technology Major Project of China. For the Chinese translation of the abstract see Supplementary Materials section.

Prevalence of Bandemia in Respiratory Viral Infections: A Pediatric Emergency Room Experience.

Objective: The aim of this study was to examine the prevalence of bandemia in confirmed respiratory viral infections in febrile infants and children presenting to the emergency department.Methods: An observational retrospective study from January 1, 2016, through December 31, 2016, was conducted in patients between the ages of ≥ 1 month and ≤ 5 years presenting to the emergency room with fever and who had a complete blood cell count performed. Patients were separated into seven groups based on the type of respiratory viral infection. Inclusion criteria strictly counted children with viral infections and absence of clinical and laboratory evidence of a bacterial coinfection.Results: A total of 419 patients had a documented viral infection. A significant proportion of these children were found to have bandemia; children with adenovirus (17%), respiratory syncytial virus (RSV) (14.9%), human metapneumovirus (hMPV) (13%), and parainfluenza virus (7.9%) had the highest prevalence when the cutoff for bandemia was set at 10%. The prevalence increased to 35.3, 30.9, 40.3, and 15.8% for adenovirus, RSV, hMPV, and parainfluenza virus, respectively, when this cutoff was lowered further to 5%.Conclusion: Band neutrophils are detected frequently in confirmed respiratory viral infections particularly during early stages.

Tackling poverty, treating obesity: a ‘whole system’ approach

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated in the outcomes of respiratory virus infections. We report...

TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated in the outcomes of respiratory virus infections. We report that RSV infection triggers necroptosis in primary mouse macrophages and human monocytes in a RIPK1-, RIPK3- and MLKL-dependent manner. Moreover, necroptosis pathways are harmful to RSV clearance from alveolar macrophages. Additionally, Ripk3−/− mice were protected from RSV-induced weight loss and presented with reduced viral loads in the lungs.Alveolar macrophage depletion also protected mice from weight loss and decreased lung RSV virus load. Importantly, alveolar macrophage depletion abolished the upregulation of Ripk3 and Mlkl gene expression induced by RSV infection in the lung tissue.Autocrine tumor necrosis factor (TNF)-mediated RSV-triggered macrophage necroptosis and necroptosis pathways were also involved in TNF secretion even when macrophages were committed to cell death, which can worsen lung injury during RSV infection. In line, Tnfr1−/− mice had a marked decrease in Ripk3 and Mlkl gene expression and a sharp reduction in the numbers of necrotic alveolar macrophages in the lungs. Finally, we provide evidence that elevated nasal levels of TNF are associated with disease severity in infants with RSV bronchiolitis.We propose that targeting TNF and/or the necroptotic machinery may be valuable therapeutic approaches to reduce the respiratory morbidity caused by RSV infection in young children.

Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins.

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016–2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

Polymerase-tagged respiratory syncytial virus reveals a dynamic rearrangement of the ribonucleocapsid complex during infection.

The ribonucleocapsid complex of respiratory syncytial virus (RSV) is responsible for both viral mRNA transcription and viral replication during infection, though little is known about how this dual function is achieved. Here, we report the use of a recombinant RSV virus with a FLAG-tagged large polymerase protein, L, to characterize and localize RSV ribonucleocapsid structures during the early and late stages of viral infection. Through proximity ligation assays and super-resolution microscopy, viral RNA and proteins in the ribonucleocapsid complex were revealed to dynamically rearrange over time, particularly between 6 and 8 hours post infection, suggesting a connection between the ribonucleocapsid structure and its function. The timing of ribonucleocapsid rearrangement corresponded with an increase in RSV genome RNA accumulation, indicating that this rearrangement is likely involved with the onset of RNA replication and secondary transcription. Additionally, early overexpression of RSV M2-2 from in vitro transcribed mRNA was shown to inhibit virus infection by rearranging the ribonucleocapsid complex. Collectively, these results detail a critical understanding into the localization and activity of RSV L and the ribonucleocapsid complex during RSV infection.