Nucleotide-Binding Oligomerization Domain 1 (NOD1) Agonists Prevent SARS-CoV-2 Infection in Human Lung Epithelial Cells through Harnessing the Innate Immune Response.

The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells.

Respiratory viral infections before the COVID-19 in Portugal: A single center study.

Objectives: We aimed to describe the respiratory viruses (RV) found in respiratory samples from patients admitted to Hospital de São Bernardo, Setúbal, Portugal, between October 2019 and March 2020, and to correlate these with clinical features. Design: This retrospective study explored 948 fresh frozen naso/oropharyngeal swabs, tested by reverse transcription-polymerase chain reaction. Results: Rhinovirus/enterovirus, influenza, and respiratory syncytial virus (hRSV) were the most prevalent RV. Half of the patients fulfilled the acute respiratory infection (ARI) and/or influenza-like illness (ILI) criteria, with increasing age significantly reducing the risk of ARI and/or ILI. Hospital admission was more frequently observed in symptomatic patients, but the length of stay and mortality were significantly lower. Most (96.5 %) patients had a main respiratory diagnosis. In adults, the most prevalent was pneumonia, which particularly affected older patients, while in children, the most common was bronchiolitis. The number of hospital admissions was high. Sudden onset, shortness of breath, older age, and hRSV detection significantly increased the risk of hospital admission overall. In bronchiolitis, female gender significantly increased the risk of hospital admission, while older age significantly reduced this risk. Twenty patients died within the first month of sampling, and all were older adults. Older age and male gender significantly increased the risk of death. Conclusions: Respiratory viral infections can have a significant clinical impact, particularly in young infants with bronchiolitis and older adults with pneumonia. This study provides the first snapshot of the respiratory viral infections just before the outbreak of SARS-CoV-2 in Portugal, providing relevant clinical insights.

Unravelling the acute respiratory infection landscape: virus type, viral load, health status and coinfection do matter.

Introduction: Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a respiratory sample is common. To better understand these viral codetections and potential interferences, we tested for the presence of viruses and developed quantitative PCR (Polymerase Chain Reaction) for the viruses most prevalent in coinfections: human rhinovirus (HRV) and respiratory syncytial virus (RSV), and quantified their viral loads according to coinfections and health status, age, cellular abundance and other variables. Materials and methods: Samples from two different cohorts were analyzed: one included hospitalized infants under 12 months of age with acute bronchiolitis (n=719) and the other primary care patients of all ages with symptoms of ARI (n=685). We performed Multiplex PCR on nasopharyngeal swabs, and quantitative PCR on samples positive for HRV or/and RSV to determine viral loads (VL). Cellular abundance (CA) was also estimated by qPCR targeting the GAPDH gene. Genotyping was performed either directly from first-line molecular panel or by PCR and sequencing for HRV. Results: The risks of viral codetection were 4.1 (IC95[1.8; 10.0]) and 93.9 1 (IC95[48.7; 190.7]) higher in infants hospitalized for bronchiolitis than in infants in primary care for RSV and HRV respectively (p<0.001). CA was higher in samples positive for multiple viruses than in mono-infected or negative samples (p<0.001), and higher in samples positive for RSV (p<0.001) and HRV (p<0.001) than in negative samples. We found a positive correlation between CA and VL for both RSV and HRV. HRV VL was higher in children than in the elderly (p<0.05), but not RSV VL. HRV VL was higher when detected alone than in samples coinfected with RSV-A and with RSV-B. There was a significant increase of RSV-A VL when codetecting with HRV (p=0.001) and when co-detecting with RSV-B+HRV versus RSV-A+ RSV-B (p=0.02). Conclusions: Many parameters influence the natural history of respiratory viral infections, and quantifying respiratory viral loads can help disentangle their contributions to viral outcome.

Role of airway epithelium in viral respiratory infections: Can carbocysteine prevent or mitigate them?

Alterations in airway epithelial homeostasis increase viral respiratory infections risk. Viral infections frequently are associated with chronic obstructive pulmonary disease (COPD) exacerbations, events that dramatically promote disease progression. Mechanism promoting the main respiratory viruses entry and virus-evocated innate and adaptive immune responses have now been elucidated, and an oxidative stress central role in these pathogenic processes has been recognized. Presence of reactive oxygen species in macrophages and other cells allows them to eliminate virus, but its excess alters the balance between innate and adaptive immune responses and proteases/anti-proteases and leads to uncontrolled inflammation, tissue damage, and hypercoagulability. Different upper and lower airway cell types also play a role in viral entry and infection. Carbocysteine is a muco-active drug with anti-oxidant and anti-inflammatory properties used for the management of several chronic respiratory diseases. Although the use of anti-oxidants has been proposed as an effective strategy in COPD exacerbations management, the molecular mechanisms that explain carbocysteine efficacy have not yet been fully clarified. The present review describes the most relevant features of the common respiratory virus pathophysiology with a focus on epithelial cells and oxidative stress role and reports data supporting a putative role of carbocysteine in viral respiratory infections.

Incidence and causative agent distribution of viral-induced paediatric asthma exacerbations under strict infection control measures: a single-centre retrospective study in Japan.

BACKGROUND: The prevalence of respiratory viruses in children changed under strict infection control measures during the coronavirus disease 2019 (COVID-19) outbreak. In this study, we investigated the frequency of viral detection in the nasopharynx of paediatric patients with asthma exacerbations requiring hospitalization during the COVID-19 pandemic, as well as the distribution of causative viruses. METHODS: We included paediatric patients admitted for asthma exacerbations between November 2020 and December 2022 at a single centre in Kobe, Japan. Demographic, clinical, and laboratory data were collected from their medical records and using additional questionnaires. All patients enrolled in this study met the diagnostic criteria for asthma exacerbations outlined in the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2020. Statistical differences were calculated using univariate analyses (chi-square or Mann‒Whitney U test). RESULTS: We enrolled 203 children hospitalized for asthma attacks and collected nasopharyngeal samples from 189 patients. The median patient age was 3.0 years. Asthma severity was classified as mild (4.0%), moderate (82.3%), or severe (13.8%). The proportion of viral respiratory infections was 95.2% (180/189). The rate of patients with multiple viral infections was 20.6% (39/189). The most frequently detected pathogens were rhinovirus and enterovirus (RV/EV) at 69.3% (131/189), allowing for duplicate detection, followed by respiratory syncytial virus (RSV) at 28.6% (54/189). We also detected RV/EV almost every month compared to RSV and other viruses. In addition, RV/EV-positive patients were significantly older (p = 0.033), exhibited higher WBC counts (p < 0.001) and higher Eos counts (p < 0.001), had elevated total IgE levels (p < 0.001) and house dust mite-specific IgE levels (p = 0.019), had a shorter duration of hospitalization (p < 0.001), and had a shorter duration of oxygen therapy (p < 0.001). In patients positive for RV/EV, the use of ICSs significantly reduced the severity of the condition (p < 0.001). CONCLUSION: Even under strict infection control measures, respiratory viruses were detected in the nasopharynx of almost all paediatric patients who had asthma exacerbations requiring hospitalization.

Systematic Evaluation of Hematologic Parameters and Blood Smear Findings in Patients With SARS-CoV-2 vs Other Viral Respiratory Infections.

OBJECTIVES: We evaluated and compared the peripheral blood findings in patients with acute COVID-19 vs other viral respiratory infections. METHODS: We retrospectively reviewed peripheral blood counts and smear morphology in patients with a positive viral respiratory panel (VRP) or SARS-CoV-2 test. RESULTS: A total of 97 peripheral blood samples (COVID-19 infection, 53; VRP positive, 44) from 50 patients (mean [SD] age, 45.8 [20.8] years; females 52%) were reviewed. There were no statistically significant differences in the demographic characteristics between the 2 groups. The most common peripheral blood abnormalities were anemia, thrombocytopenia, absolute lymphopenia, and reactive lymphocytes. The following peripheral blood findings were significantly associated with other viral respiratory infections compared with COVID-19 infection: low red blood cell count, low hematocrit, high mean corpuscular volume, thrombocytopenia, low mean platelet volume, high red cell distribution width, band neutrophilia, and toxic granulation in neutrophils. CONCLUSIONS: Our study showed that there are several peripheral blood count and morphologic abnormalities seen in patients with COVID-19, but most of these findings lack specificity as they are also seen in the other viral respiratory infections.

Maternal respiratory viral infections during pregnancy and offspring's neurodevelopmental outcomes: A systematic review.

Maternal infections during pregnancy, as cytomegalovirus and zika, have been consistently associated with severe newborn neurodevelopmental conditions, mainly related to vertical transmission and congenital infection. However, little is known about the neurodevelopmental consequences of maternal respiratory viral infections, which are the most prevalent infections during pregnancy. The recent COVID-19 pandemic has increased the interest in understanding the consequences of infections in offspring's development. This systematic review explores whether maternal gestational viral respiratory infections are associated with neurodevelopmental deviations in children below 10 years-old. The search was conducted in Pubmed, PsychInfo and Web of Science databases. 13 articles were revised, including information about maternal infection (Influenza, SARS-CoV-2 and unspecified respiratory infections) and offspring's neurodevelopment (global development, specific functions, temperament and behavioral/emotional aspects). Controversial results were reported regarding maternal respiratory infections during pregnancy and infants' neurodevelopment. Maternal infections seem to be associated with subtle alterations in some offspring's developmental subdomains, as early motor development, and attentional, behavioral/emotional minor problems. Further studies are needed to determine the impact of other psychosocial confounding factors.

Characteristics of infections and their risk factors in children with biliary atresia.

BACKGROUND: Children with biliary atresia (BA) may experience various infections (e.g., cholangitis, bacteremia, and viral respiratory infections (VRI)) throughout their disease course. This study aimed to identify and describe these infections and their risk factors for development in children with BA. METHODS: This retrospective observational study identified infections in children with BA using predefined criteria, including VRI, bacteremia with and without central line (CL), bacterial peritonitis, positive stool pathogens, urinary tract infections, and cholangitis. Infections were identified until liver transplant, death or last follow-up with native liver. Infection-free survival was estimated by Kaplan-Meier analysis. Logistic regression was used to estimate odds of infection per clinical characteristics. Cluster analysis was performed to identify patterns of infection development. RESULTS: 48 of 65 (73.8%) children had ≥1 infection during their disease course (mean length of follow up: 40.2 months). Cholangitis (n = 30) and VRI (n = 21) were most common. Nearly half (45%) of all infections developed within 3-months of Kasai hepatoportoenterostomy. Kasai performed ≥45 days of life was associated with 3.5-fold increased risk of any infection (95% CI 1.2-11.4). Risk of VRI was inversely related to platelet count at 1-month post-Kasai (OR 0.5, 0.19-0.99). Cluster analysis of infectious patterns identified three unique cohorts of patients based on their infection history: no/few infections (n = 18), mostly cholangitis (n = 20) or mixed infections (n = 27). CONCLUSION: Variability of infection risk exists amongst children with BA. Age at Kasai and platelet count are risk factors for future infections, suggesting that patients with more severe disease are at greater risk. Cirrhosis associated immune deficiency may exist in chronic pediatric liver disease and should be the subject of future investigations in order to optimize outcomes.

In Vitro Antiviral and Anti-Inflammatory Activities of N-Acetylglucosamine: Development of an Alternative and Safe Approach to Fight Viral Respiratory Infections.

Viral respiratory tract infections (RTIs) are responsible for significant morbidity and mortality worldwide. A prominent feature of severe respiratory infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is the cytokine release syndrome. Therefore, there is an urgent need to develop different approaches both against viral replication and against the consequent inflammation. N-acetylglucosamine (GlcNAc), a glucosamine (GlcN) derivative, has been developed as an immunomodulatory and anti-inflammatory inexpensive and non-toxic drug for non-communicable disease treatment and/or prevention. Recent studies have suggested that GlcN, due to its anti-inflammatory activity, could be potentially useful for the control of respiratory virus infections. Our present study aimed to evaluate in two different immortalized cell lines whether GlcNAc could inhibit or reduce both viral infectivity and the inflammatory response to viral infection. Two different viruses, frequent cause of upper and lower respiratory tract infections, were used: the H1N1 Influenza A virus (IAV) (as model of enveloped RNA virus) and the Human adenovirus type 2 (Adv) (as model of naked DNA virus). Two forms of GlcNAc have been considered, bulk GlcNAc and GlcNAc in nanoform to overcome the possible pharmacokinetic limitations of GlcNAc. Our study suggests that GlcNAc restricts IAV replication but not Adv infection, whereas nano-GlcNAc inhibits both viruses. Moreover, GlcNAc and mainly its nanoformulation were able to reduce the pro-inflammatory cytokine secretion stimulated by viral infection. The correlation between inflammatory and infection inhibition is discussed.

Preschool-Aged Household Contacts as a Risk Factor for Viral Respiratory Infections in Healthcare Personnel.

Background: Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings. Methods: We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011-2012 to 2014-2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0-5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction-detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level. Results: Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05-1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09-1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts. Conclusions: Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings.

Using Discarded Facial Tissues to Monitor and Diagnose Viral Respiratory Infections.

Molecular biology amplification enables sensitive detection of most respiratory viruses through nasopharyngeal swabbing. We developed an innovative approach to detect viral genomes on used facial tissues. In 2 communities of children, used tissues were collected once weekly for 1 year. Pooled analysis of tissues enabled detection of successive virus circulation in 4 age groups over time and forecasted by several weeks the circulation of influenza in the general population. At the individual level, in a proof-of-concept study of 30 volunteers with influenza-like signs/symptoms, we identified common respiratory viruses. The signals for SARS-CoV-2 obtained in parallel from 15 facial tissues and swab samples were similar and often higher for the tissues (11/15). Individual analysis of tissues offers a noninvasive, sensitive, and affordable alternative to self-sampling without a medical care requirement. Pooled analyses may be used to detect virus spread in specific communities, predict seasonal epidemics, and alert the population to viral infections.

Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections.

Acute and chronic lower airway disease still represent a major cause of morbidity and mortality on a global scale. With the steady rise of multidrug-resistant respiratory pathogens, such as Pseudomonas aeruginosa and Klebsiella pneumoniae, we are rapidly approaching the advent of a post-antibiotic era. In addition, potentially detrimental novel variants of respiratory viruses continuously emerge with the most prominent recent example being severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To this end, alternative preventive and therapeutic intervention strategies will be critical to combat airway infections in the future. Chronic respiratory diseases are associated with alterations in the lung and gut microbiome, which is thought to contribute to disease progression and increased susceptibility to infection with respiratory pathogens. In this review we will focus on how modulating and harnessing the microbiome may pose a novel strategy to prevent and treat pulmonary infections as well as chronic respiratory disease.

Infections respiratoires aigües virales chez les enfants de moins de 15 ans à Conakry: étiologies et prise en charge / Acute viral respiratory infections of children aged 0-15 years in the city of Conakry: aetiologies and management

Introduction. Les infections respiratoires aiguës (IRA) sont des pathologies ubiquitaires très fréquentes, touchant aussi bien les adultes que les enfants. L'inclusion des vaccins conjugués, contre les pneumocoques et l'Haemophilus influenzae type B a modifié l'épidémiologie en réduisant la prévalence de ces bactéries dans les atteintes infectieuses respiratoires, la prédominance virale est devenue la règle. Notre travail avait pour objectif d'identifier les principaux virus responsables d'IRAS chez les enfants au service de pédiatrie de Donka de décrire la prise en charge des enfants. Patients et méthodes. Étude descriptive prospective de 6 mois allant du 01 Avril au 30 Septembre 2022 incluant les enfants admis au service pour IRAS dont une PCR a été réalisée sur prélèvement nasopharyngé. Résultats. Une proportion de 3,3% des 1584 enfants avaient une IRA virale. 51,1% avaient moins de 5 ans. La proportion des filles était de 63,05% et 76,09% des enfants étaient vaccinés selon le programme élargi de vaccination (PEV). Les motifs de consultation les plus fréquents étaient : fièvre, difficulté respiratoire, asthénie physique, myalgie et toux. La bronchiolite était le diagnostic le plus fréquent. Le diagnostic clinique et radiologique était dominé par la bronchiolite, la bronchopneumonie et la pneumonie. La PCR était positive dans 3,26% des cas dont 2/3 pour le virus influenza et 1/3 pour le coronavirus. Le paracétamol, l'oxygénation, l'antibiothérapie et le sérum physiologique dominaient le traitement. Conclusion. La prévalence des IRA reste élevée avec une faible implication virale. Une étude plus poussée comprenant la microbiologie des prélèvements nasopharyngés et la PCR est nécessaire

Introduction. Acute respiratory infections (ARI) are very common ubiquitous pathologies, affecting both adults and children. The inclusion of conjugate vaccines, against pneumococci and Haemophilus influenzae type b, has changed the epidemiology by reducing the prevalence of these bacteria in respiratory infectious diseases, viral predominance has become the rule. The aim of our study was to identify the main viruses responsible for ARI in children at the Donka Pediatric Department and to secribe the management of patients. Patients and methods. This was a prospective descriptive study of 6 months from 01 April to 30 September 2022 including children admitted to the service for IRAS whose PCR was performed on nasopharyngeal swab. Results. A proportion of 3.3% of the 1584 children had viral SARI. 51.1% were under 5 years of age. The proportion of girls was 63.05% and 76.09% of children were vaccinated according to the EPI. The most common reasons for consultations were fever, difficulty breathing, physical asthenia, myalgia and cough. Bronchiolitis was the most common diagnosis, Clinical and radiological diagnosis was dominated by bronchiolitis, bronchopneumonia and pneumonia. PCR was positive in 3.26% of cases including 2/3 for influenza virus and 1/3 for coronavirus. Paracetamol, oxygenation, antibiotic therapy and saline dominated treatment. Conclusion. The prevalence of SARI remains high with low viral involvement. Further study including bacteriology of nasopharyngeal specimens and PCR is needed

Impact of the French National Lockdown on Admissions to 14 Pediatric Intensive Care Units During the 2020 COVID-19 Pandemic-A Retrospective Multicenter Study.

Background: After the COVID-19 pandemic reached France in January 2020, a national lockdown including school closures was officially imposed from March 17, 2020, to May 10, 2020. Pediatric intensive care units (PICUs) admit critically ill infants, children and teenagers with severe acute conditions, in particular infectious and traumatic diseases. We hypothesized that PICU admissions would be considerably modified by the lockdown. Aims: The objectives of the study were to describe the type of admissions to French PICUs and to compare the occupation of PICU beds according to local epidemic conditions during the French national lockdown period, compared with the same period the previous year. Methods: We conducted a retrospective multicenter study in 14 French PICUs. All children aged from 7 days to 18 years admitted to one of the 14 participating PICUs over two 3-month period (March 1, 2020, to May 31, 2020 and March 1, 2019, to May 31, 2019) were included. Analysis was based on data extracted from the medicalized information systems program (a national database used in all French hospitals, into which all admissions and their diagnoses are coded for the purpose of calculating hospital funding). Each main diagnosis was reclassified in 13 categories, corresponding to normal PICU admissions. Results: We analyzed a total of 3,040 admissions, 1,323 during the 2020 study period and 1,717 during the same period in 2019. Total admissions decreased by 23% [incidence rate ratio (IRR) 0.77, 95% CI 0.71-0.83, p < 0.001], in particular for viral respiratory infections (-36%, IRR 0.64, 95% CI 0.44-0.94, p = 0.001). Admissions for almost all other diagnostic categories decreased, except intoxications and diabetes which increased, while admissions for cardiac and hemodynamic disorders were stable. Patient age and the sex ratio did not differ between the two periods. Median length of stay in the PICU was longer in 2020 [4 (IQR 2-9) vs. 3 (IQR 1-8) days, p = 0.002] in 2019. Mortality remained stable. Conclusions: In this large national study, we showed a decrease in the number of PICU admissions. The most severe patients were still admitted to intensive care and overall mortality remained stable.

Frequency of serious bacterial infections in young infants with and without viral respiratory infections.

BACKGROUND: The goal of our investigation was to describe the incidence of serious bacterial infection (SBI, defined as bacteremia, urinary tract infection (UTI), or meningitis) in young infants with and without documented viral pathogens. METHODS: This was a retrospective cross-sectional study (1/2016-12/2017) in 3 emergency departments (EDs). Previously healthy 0-60-day-old infants were included if at least respiratory viral testing and a blood culture was obtained. The frequency of SBI, the primary outcome, was compared among infants with/without respiratory viral infections using the Pearson Chi-square test (or Fisher's Exact Test) and unadjusted odds ratios (OR). RESULTS: The median age of the 597-infant cohort was 32 days (interquartile range: 20-45 days); 42% were female. Eighty-three percent were well appearing in the ED and 72% were admitted. ED triage vitals commonly revealed tachypnea (68%), pyrexia (45%), and tachycardia (28%); hypoxemia (5%) was uncommon. Twenty-eight percent had positive viral testing, most commonly RSV (93/169, 55%), parainfluenza (29, 17%), and influenza A (23, 14%). Eighty-three infants (13.9%) had SBI: 8.4% (n = 50) had UTI alone, 2.8% (n = 17) had bacteremia alone, 1.2% (n = 7) had bacteremia + UTI, 1.0% (n = 6) had bacteremia + meningitis, and 0.5% (n = 3) had meningitis alone. Infants with documented respiratory viral pathogens were less likely to have any SBI (OR: 0.23; 95% CI: 0.11-0.50), UTI (OR 0.22, 95% CI: 0.09-0.56), or bacteremia (OR 0.27, 95% CI: 0.08-0.9) than infants with negative viral testing. There was no difference in meningitis frequency based on viral status (OR: 0.13, 95% CI: 0.008-2.25). CONCLUSIONS: The frequency of bacteremia and UTI was lower in young infants with respiratory viral infections compared to infants with negative respiratory viral testing.

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.

Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.

COVID-19 Shuts Doors to Flu but Keeps Them Open to Rhinoviruses.

It is well known that rhinoviruses are distributed across the globe and are the most common cause of the common cold in all age groups. Rhinoviruses are widely considered to be harmless because they are generally perceived as respiratory viruses only capable of causing mild disease. However, they may also infect the lower respiratory tract, inducing chronic obstructive pulmonary disease and exacerbations of asthma, bronchiolitis, etc. The role of rhinoviruses in pathogenesis and the epidemiological process is underestimated, and they need to be intensively studied. In the light of recent data, it is now known that rhinoviruses could be one of the key epidemiological barriers that may influence the spread of influenza and novel coronaviruses. It has been reported that endemic human rhinoviruses delayed the development of the H1N1pdm09 influenza pandemic through viral interference. Moreover, human rhinoviruses have been suggested to block SARS-CoV-2 replication in the airways by triggering an interferon response. In this review, we summarized the main biological characteristics of genetically distinct viruses such as rhinoviruses, influenza viruses, and SARS-CoV-2 in an attempt to illuminate their main discrepancies and similarities. We hope that this comparative analysis will help us to better understand in which direction research in this area should move.

Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don't have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

Invasive Aspergillosis After Influenza and Other Viral Respiratory Infections Among Intensive Care Unit Patients in a Commercially Insured Population in the United States, 2013-2018.

Influenza-associated aspergillosis (IAA) is an emerging phenomenon in intensive care unit patients with severe influenza. In a large US health insurance claims database, IAA was uncommon (0.3%) during 2013-2018. The low IAA frequency likely reflects underdiagnosis and differences in medical practices or epidemiologic differences.

Time Distributions of Common Respiratory Pathogens Under the Spread of SARS-CoV-2 Among Children in Xiamen, China.

Objectives: The aim of this study was to observe the effect of COVID-19 prevention and control measures on the transmission of common respiratory viruses in a pediatric population. Methods: This was a retrospective observational study. The study population was selected from children with respiratory diseases who attended Xiamen Children's Hospital from January 1, 2018 to January 31, 2021. All children were screened for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), adenovirus, and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The changes in respiratory virus detection rates before and after the SARS-CoV-2 intervention were analyzed using an interrupted time-series model. Polynomial curve fitting was also used to predict future short-term trends in respiratory virus detection. Results: A total of 56,859 children were seen at Xiamen Children's Hospital from January 1, 2018 to Jan 31, 2021, of which 32,120 were tested for respiratory viruses via pharyngeal swabs. The overall positive detection rates of the four respiratory viral infections decreased significantly (P = 0.0017) after the implementation of the quarantine and school suspension measures in January 2020. Among them, the detection rate of RSV decreased most significantly (P = 0.008), and although there was no statistically significant difference in the detection rates of the influenza virus, parainfluenza virus, and adenovirus, a downward trend in the graph was observed. The positive detection rates of RSV in the 0-1-, 1-3-, and 3-7-year-old groups all decreased significantly (P = 0.035, 0.016, and 0.038, respectively). The change in the positive detection rate of RSV was relatively stable in the 7-18-year-old group. A total of 10,496 samples were tested for SARS-CoV-2, and no positive cases were reported. Conclusions: The combination of preventive and control measures for COVID-19 reduced the detection rate of four common respiratory viruses, with the greatest impact on RSV. If prevention and control measures continue to be maintained, the overall detection rate or absolute number of detections for the four respiratory viruses will remain low in the short term. However, this trend is likely to vary with the changes in measures.