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Frontiers in Immunology 2024Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several...
INTRODUCTION
Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied.
METHODS
Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group.
RESULTS
We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8 T cells and memory precursor effector CD8 T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level.
DISCUSSION
To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.
Topics: Child; Mice; Humans; Animals; Child, Preschool; Aged; Metapneumovirus; CD8-Positive T-Lymphocytes; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Paramyxoviridae Infections; Adaptive Immunity; Respiratory Tract Infections; Inflammation; Immunoglobulin A
PubMed: 38404579
DOI: 10.3389/fimmu.2024.1330209 -
Children (Basel, Switzerland) Feb 2024Antibiotics are frequently prescribed to children with pneumonia, although viruses are responsible for most cases. We aimed to evaluate the impact of multiplex...
Antibiotics are frequently prescribed to children with pneumonia, although viruses are responsible for most cases. We aimed to evaluate the impact of multiplex polymerase chain reaction (mPCR) on antibiotic use. We conducted a prospective study of children under 14 years of age admitted for suspected viral pneumonia, from October 2019 to June 2022 (except March-November 2020). A mPCR respiratory panel (FilmArray 2, bioMérieux, Marcy-l'Étoile, France) was performed within 72 h of admission. Patients with positive reverse transcription PCR for respiratory syncytial virus, influenza, or SARS-CoV-2 were excluded. We compared the patients with historical controls (2017-2018) who had suspected viral pneumonia but did not undergo an aetiological study. We included 64 patients and 50 controls, with a median age of 26 months. The respiratory panel detected viral pathogens in 55 patients (88%), including 17 (31%) with co-infections. Rhinovirus/enterovirus ( = 26) and human metapneumovirus ( = 22) were the most common pathogens, followed by adenovirus and parainfluenza ( = 10). There were no statistically significant differences in the total antibiotic consumption (83% of cases and 86% of controls) or antibiotics given for ≥72 h (58% vs. 66%). Antibiotics were prescribed in 41% of the cases and 72% of the controls at discharge ( = 0.001). Ampicillin was the most commonly prescribed antibiotic among the patients (44% vs. 18% for controls, = 0.004), while azithromycin was the most commonly prescribed among the controls (19% vs. 48% for patients and controls, respectively; = 0.001). Our findings underscore the need for additional interventions alongside molecular diagnosis to reduce antibiotic usage in paediatric community-acquired pneumonia.
PubMed: 38397359
DOI: 10.3390/children11020245 -
Scientific Reports Feb 2024Respiratory viral infections, a major public health concern, necessitate continuous development of novel antiviral strategies, particularly in the face of emerging and...
Respiratory viral infections, a major public health concern, necessitate continuous development of novel antiviral strategies, particularly in the face of emerging and re-emerging pathogens. In this study, we explored the potential of human milk oligosaccharides (HMOs) as broad-spectrum antiviral agents against key respiratory viruses. By examining the structural mimicry of host cell receptors and their known biological functions, including antiviral activities, we assessed the ability of HMOs to bind and potentially inhibit viral proteins crucial for host cell entry. Our in silico analysis focused on viral proteins integral to host-virus interactions, namely the hemagglutinin protein of influenza, fusion proteins of respiratory syncytial and human metapneumovirus, and the spike protein of SARS-CoV-2. Using molecular docking and simulation studies, we demonstrated that HMOs exhibit varying binding affinities to these viral proteins, suggesting their potential as viral entry inhibitors. This study identified several HMOs with promising binding profiles, highlighting their potential in antiviral drug development. This research provides a foundation for utilizing HMOs as a natural source for designing new therapeutics, offering a novel approach in the fight against respiratory viral infections.
Topics: Humans; Antiviral Agents; Viral Proteins; Molecular Docking Simulation; Milk, Human; SARS-CoV-2; Influenza, Human; Oligosaccharides
PubMed: 38374384
DOI: 10.1038/s41598-024-54624-6 -
The Lancet. Microbe Apr 2024There has been high uptake of rapid antigen test device use for point-of-care COVID-19 diagnosis. Individuals who are symptomatic but test negative on COVID-19 rapid...
BACKGROUND
There has been high uptake of rapid antigen test device use for point-of-care COVID-19 diagnosis. Individuals who are symptomatic but test negative on COVID-19 rapid antigen test devices might have a different respiratory viral infection. We aimed to detect and sequence non-SARS-CoV-2 respiratory viruses from rapid antigen test devices, which could assist in the characterisation and surveillance of circulating respiratory viruses in the community.
METHODS
We applied archival clinical nose and throat swabs collected between Jan 1, 2015, and Dec 31, 2022, that previously tested positive for a common respiratory virus (adenovirus, influenza, metapneumovirus, parainfluenza, rhinovirus, respiratory syncytial virus [RSV], or seasonal coronavirus; 132 swabs and 140 viral targets) on PCR to two commercially available COVID-19 rapid antigen test devices, the Panbio COVID-19 Ag Rapid Test Device and Roche SARS-CoV-2 Antigen Self-Test. In addition, we collected 31 COVID-19 rapid antigen test devices used to test patients who were symptomatic at The Royal Melbourne Hospital emergency department in Melbourne, Australia. We extracted total nucleic acid from the device paper test strips and assessed viral recovery using multiplex real-time PCR (rtPCR) and capture-based whole genome sequencing. Sequence and genome data were analysed through custom computational pipelines, including subtyping.
FINDINGS
Of the 140 respiratory viral targets from archival samples, 89 (64%) and 88 (63%) were positive on rtPCR for the relevant taxa following extraction from Panbio or Roche rapid antigen test devices, respectively. Recovery was variable across taxa: we detected influenza A in nine of 18 samples from Panbio and seven of 18 from Roche devices; parainfluenza in 11 of 20 samples from Panbio and 12 of 20 from Roche devices; human metapneumovirus in 11 of 16 from Panbio and 14 of 16 from Roche devices; seasonal coronavirus in eight of 19 from Panbio and two of 19 from Roche devices; rhinovirus in 24 of 28 from Panbio and 27 of 28 from Roche devices; influenza B in four of 15 in both devices; and RSV in 16 of 18 in both devices. Of the 31 COVID-19 devices collected from The Royal Melbourne Hospital emergency department, 11 tested positive for a respiratory virus on rtPCR, including one device positive for influenza A virus, one positive for RSV, four positive for rhinovirus, and five positive for SARS-CoV-2. Sequences of target respiratory viruses from archival samples were detected in 55 (98·2%) of 56 samples from Panbio and 48 (85·7%) of 56 from Roche rapid antigen test devices. 98 (87·5%) of 112 viral genomes were completely assembled from these data, enabling subtyping for RSV and influenza viruses. All 11 samples collected from the emergency department had viral sequences detected, with near-complete genomes assembled for influenza A and RSV.
INTERPRETATION
Non-SARS-CoV-2 respiratory viruses can be detected and sequenced from COVID-19 rapid antigen devices. Recovery of near full-length viral sequences from these devices provides a valuable opportunity to expand genomic surveillance programmes for public health monitoring of circulating respiratory viruses.
FUNDING
Australian Government Medical Research Future Fund and Australian National Health and Medical Research Council.
Topics: Humans; COVID-19; SARS-CoV-2; Influenza, Human; COVID-19 Testing; Australia; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus, Human; Whole Genome Sequencing
PubMed: 38359857
DOI: 10.1016/S2666-5247(23)00375-0 -
Cureus Jan 2024Human metapneumovirus (HMPV) is an important cause of seasonal respiratory tract infections, mainly in children and immunocompromised adults. The use of the Charlson...
INTRODUCTION
Human metapneumovirus (HMPV) is an important cause of seasonal respiratory tract infections, mainly in children and immunocompromised adults. The use of the Charlson Comorbidity Index (CCI) to predict outcomes in hospitalized patients has been validated in several settings.
OBJECTIVE
This study aims to describe the clinical characteristics of adult patients with HMPV infection and evaluate the value of the CCI in predicting outcomes in patients with acute HMPV infections requiring hospitalization.
METHOD
This is a single-center case-series study of hospitalized patients with HMPV infection in 2017.
RESULTS
Twenty-two adult patients with a mean age of 65 years were reviewed. The mean CCI was 4.6±2.6. The overall mortality was 22%. An abnormal chest X-ray (CXR) was reported in 15 patients. CCI was not different between survivors and non-survivors. Non-survivors were more likely to have abnormal CXR and a higher fever at the time of diagnosis, required mechanical ventilation, or had other concomitant infections.
CONCLUSION
The average CCI was 4.5, which was not significantly different between survivors and non-survivors. The mortality rate was elevated by 22% and was likely associated with admission to the ICU as well as the presence of another concomitant infection.
PubMed: 38357041
DOI: 10.7759/cureus.52321 -
Human Vaccines & Immunotherapeutics Dec 2024
Topics: mRNA Vaccines; Metapneumovirus; Viral Vaccines; Epitopes
PubMed: 38319127
DOI: 10.1080/21645515.2024.2311974 -
PLoS Pathogens Feb 2024Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and...
Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and both neutralizing antibodies and T cells contribute to protection. However, little is known about mechanisms of pathogenesis and most published work is based on a few extensively passaged, laboratory-adapted strains of HMPV. In this study, we isolated and characterized a panel of low passage HMPV clinical isolates representing all four genetic subgroups. The clinical isolates exhibited lower levels of in vitro replication compared to a lab-adapted strain. We compared disease phenotypes using a well-established mouse model. Several virulent isolates caused severe weight loss, lung pathology, airway dysfunction, and fatal disease in mice, which was confirmed in three inbred mouse strains. Disease severity did not correlate with lung viral titer, as virulent strains exhibited restricted replication in the lower airway. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production and neutrophil influx; however, depletion of neutrophils or genetic ablation of inflammasome components did not reverse disease. Virulent clinical isolates induced markedly increased type I and type III interferon (IFN) secretion in vitro and in vivo. STAT1/2-deficient mice lacking both type I and type III IFN signaling showed reduced disease severity and increased lung viral replication. Inhibition of type I IFN signaling using a blocking antibody or genetic ablation of the type I IFN receptor reduced pathology with minimal effect on viral replication. Conversely, blockade of type III IFN signaling with a neutralizing antibody or genetic ablation of the IFN-lambda receptor had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV pathogenesis and immunity.
Topics: Child; Animals; Mice; Humans; Metapneumovirus; Interferon Lambda; Paramyxoviridae Infections; Lung; Respiratory Tract Infections; Interferons
PubMed: 38315735
DOI: 10.1371/journal.ppat.1011840 -
Frontiers in Cellular and Infection... 2023Respiratory viral infection (RVI) is of very concern after the outbreak of COVID-19, especially in pediatric departments. Learning pathogen spectrum of RVI in children...
INTRODUCTION
Respiratory viral infection (RVI) is of very concern after the outbreak of COVID-19, especially in pediatric departments. Learning pathogen spectrum of RVI in children previous the epidemic of COVID-19 could provide another perspective for understanding RVI under current situation and help to prepare for the post COVID-19 infection control.
METHODS
A nucleic acid sequence-based amplification (NASBA) assay, with 19 pairs of primers targeting various respiratory viruses, was used for multi-pathogen screening of viral infections in children presenting influenza-like illness (ILI) symptoms. Children with ILI at the outpatient department of Beijing Tsinghua Changgung Hospital during the influenza epidemic from 12/2018 to 01/2019 were included. Throat swabs were obtained for both the influenza rapid diagnostic test (IRDT) based on the colloidal gold immunochromatographic assay and the NASBA assay, targeting various respiratory viruses with an integrated chip technology.
RESULTS AND DISCUSSION
Of 519 patients, 430 (82.9%) were positive in the NASBA assay. The predominant viral pathogens were influenza A H1N1 pdm1/2009 (pH1N1) (48.4%) and influenza A (H3N2) (18.1%), followed by human metapneumovirus (hMPV) (8.8%) and respiratory syncytial virus (RSV) (6.1%). Of the 320 cases identified with influenza A by NASBA, only 128 (40.0%) were positive in the IRDT. The IRDT missed pH1N1 significantly more frequently than A (H3N2) (P<0.01). Influenza A pH1N1 and A (H3N2) were the major pathogens in <6 years and 6-15 years old individuals respectively (P<0.05). In summary, influenza viruses were the major pathogens in children with ILI during the 2018-2019 winter influenza epidemic, while hMPV and RSV were non-negligible. The coexistence of multiple pathogen leading to respiratory infections is the normalcy in winter ILI cases.
Topics: Child; Humans; Infant; Influenza, Human; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Virus Diseases; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; COVID-19
PubMed: 38304460
DOI: 10.3389/fcimb.2023.1351814 -
Frontiers in Pediatrics 2023The management of respiratory viruses prior to hematopoietic cell transplant (HCT) can be controversial and requires special consideration of host factors, transplant... (Review)
Review
The management of respiratory viruses prior to hematopoietic cell transplant (HCT) can be controversial and requires special consideration of host factors, transplant parameters, and the specific respiratory virus (RV). In the setting of adenovirus (ADV), human metapneumovirus (HMPV), influenza, parainfluenza virus (PIV), and respiratory syncytial virus (RSV) detection prior to hematopoietic cell transplant (HCT), clinical practice guidelines recommend transplant delay when possible; however, there is much more ambiguity when other respiratory viruses, such as seasonal coronaviruses (CoVs), human rhinovirus (HRV), and SARS-CoV-2, are detected. Our aims for this review include detailing clinical practical guidelines and reviewing current literature on pre-transplant respiratory viral infections (RVIs), including antiviral therapies and prevention strategies, when available. We will center our discussion on three representative clinical scenarios, with the goal of providing practical guidance to clinicians.
PubMed: 38304442
DOI: 10.3389/fped.2023.1339239 -
Microbiology Spectrum Mar 2024This exploratory analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with...
UNLABELLED
This exploratory analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, = 302) and May 2021 to October 2021 (Phase 3, = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups.
IMPORTANCE
Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Coinfection; Pandemics; RNA; Cytidine; Hydroxylamines
PubMed: 38299867
DOI: 10.1128/spectrum.03563-23