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ABSTRACT Growing evidence indicates that gut and respiratory microbiota have a potential key effect on bronchiolitis, mainly caused by respiratory syncytial virus (RSV). This was a prospective study of 96 infants comparing infants with bronchiolitis (n = 57, both RSV and non-RSV associated) to a control group (n = 39). Gut (feces) and respiratory [nasopharyngeal aspirate (NPA)] microbial profiles were analyzed by 16S rRNA amplicon sequencing, and respiratory viruses were identified by PCR. Clinical data of the acute episode and follow-up during the first year after infection were recorded. Pairwise comparisons showed significant differences in the gut (R2 = 0.0639, P = 0.006) and NPA (R2 = 0.0803, P = 0.006) microbiota between cases and controls. A significantly lower gut microbial richness and an increase in the NPA microbial diversity (mainly due to an increase in Haemophilus, Streptococcus, and Neisseria) were observed in the infants with bronchiolitis, in those with the most severe symptoms, and in those who subsequently developed recurrent wheezing episodes after discharge. In NPA, the higher microbial richness differed significantly between the control group and the non-RSV bronchiolitis group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001). In the gut, the richness differed significantly between the control group and the non-RSV group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001), with higher diversity in the RSV group. A distinct respiratory and intestinal microbial pattern was observed in infants with bronchiolitis compared with controls. The presence of RSV was a main factor for dysbiosis. Lower gut microbial richness and increased respiratory microbial diversity were associated with respiratory morbidity during follow-up.IMPORTANCEBoth the intestinal and respiratory microbiota of children with bronchiolitis, especially those with respiratory syncytial virus infection, are altered and differ from that of healthy children. The microbiota pattern in the acute episode could identify those children who will later have other respiratory episodes in the first year of life. Preventive measures could be adopted for this group of infants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects various mammalian species, with farmed minks experiencing the highest number of outbreaks. In Spain, we analyzed 67 whole genome sequences and eight spike sequences from 18 outbreaks, identifying four distinct lineages: B.1, B.1.177, B.1.1.7, and AY.98.1. The potential risk of transmission to humans raises crucial questions about mutation accumulation and its impact on viral fitness. Sequencing revealed numerous not-lineage-defining mutations, suggesting a cumulative mutation process during the outbreaks. We observed that the outbreaks were predominantly associated with different groups of mutations rather than specific lineages. This clustering pattern by the outbreaks could be attributed to the rapid accumulation of mutations, particularly in the ORF1a polyprotein and in the spike protein. Notably, the mutations G37E in NSP9, a potential host marker, and S486L in NSP13 were detected. Spike protein mutations may enhance SARS-CoV-2 adaptability by influencing trimer stability and binding to mink receptors. These findings provide valuable insights into mink coronavirus genetics, highlighting both host markers and viral transmission dynamics within communities.

Abstract Background Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age. Methods Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6–7-year-old children, was also employed. Results A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5–6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051–7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20–9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284–0.918, p:0.025). Conclusions Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.

Abstract Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.

Abstract The main objective was to evaluate the viability of the SARS-CoV-2 viral particles excreted in stools. In addition, we aimed to identify clinical factors associated with the detection of SARS-CoV-2 RNA in feces, and to determine if its presence is associated with an unfavorable clinical outcome, defined as intensive care unit (ICU) admission and/or death. A prospective multicenter cohort study of COVID-19 adult patients, with confirmed SARS-CoV-2 infection by RT-PCR assay in nasopharyngeal (NP) swabs admitted to four hospitals in Spain, from March 2020 to February 2021. Sixty-two adult COVID-19 patients had stool samples collected at admission and/or during the follow up, with a total of 79 stool samples. SARS-CoV-2 RNA was detected in stool samples from 27 (43.5%) out of the 62 patients. Replicative virus, measured by the generation of cytopathic effect in cell culture and subsequent RT-PCR confirmation of a decrease in the Ct values, was not found in any of these stool samples. Fecal virus excretion was not associated with the presence of gastrointestinal symptoms, or with differences in the evolution of COVID-19 patients. Our results suggest that SARS-CoV-2 replicative capacity is null or very limited in stool samples, and thus, the fecal–oral transmission of SARS-CoV-2 as an alternative infection route is highly unlikely. In our study, the detection of SARS-CoV-2 RNA in feces at the beginning of the disease is not associated with any clinical factor nor with an unfavorable clinical outcome.

Abstract Our main objective was to compare the lung function, the rate of allergic sensitization and the prevalence of asthma at 7–9 years in children hospitalized for bronchiolitis with viral coinfection versus single viral infection. Observational study in children with previous bronchiolitis and current age 7–9 years. Clinical data were collected. Fraction of exhaled nitric oxide (FeNO) determination, spirometry and skin prick test for common aeroallergens were performed. A total of 181 children hospitalized for bronchiolitis (40 coinfections and 141 single infections), with median age of 8.3 years (IQR:7.5–9.1) were included. Single-HRV-infections showed lower basal FEV1(%) than coinfections (p = 0.04) and lower z-score FEV1 than single-RSV-infections (p = 0.04) or coinfections (p = 0.02). Also, single-HRV-infections had lower post-bronchodilator FEV1(%) and z-score FEV1 values than coinfections (p = 0.03 and p = 0.03). Single-HRV-bronchiolitis was an independent risk factor for FEV1 25 ppb was detected in 21(12.5%) cases, without differences between viral groups (p = 0.768). The prevalence of allergic sensitization was similar in coinfections (31.4%) versus single infections (38.7%), (p = 0.428). The highest frequency of allergic rhinitis was observed in single-HRV patients (p = 0.004). The respiratory morbidity at 7–9 years of coinfected patients was similar to the single-HRV ones. In contrast, the likelihood of current asthma was up to 5 times higher in RSV/HRV coinfections than in the single-RSV-infections ones (p = 0.012). The respiratory morbidity at 7–9 years of age after severe bronchiolitis is significantly higher in single-HRV or viral coinfection patients that in single-RSV ones. Single-HRV-bronchiolitis is independently associated with lower lung function at school-age.

Bronchiolitis is a viral respiratory infection, with respiratory syncytial virus (RSV) being the most frequent agent, requiring hospitalization in 1% of affected children. However, there continues to be a noteworthy incidence of antibiotic prescription in this setting, further exacerbating the global issue of antibiotic resistance. This study, conducted at Severo Ochoa Hospital in Madrid, Spain, focused on antibiotic usage in children under 2 years of age who were hospitalized for bronchiolitis between 2004 and 2022. In that time, 5438 children were admitted with acute respiratory infection, and 1715 infants (31.5%) with acute bronchiolitis were included. In total, 1470 (87%) had a positive viral identification (66% RSV, 32% HRV). Initially, antibiotics were prescribed to 13.4% of infants, but this percentage decreased to 7% during the COVID-19 pandemic thanks to adherence to guidelines and the implementation of rapid and precise viral diagnostic methods in the hospital. HBoV- and HAdV-infected children and those with viral coinfections were more likely to receive antibiotics in the univariate analysis. A multivariate logistic regression analysis revealed a statistically independent association between antibiotic prescription and fever > 38 °C (p < 0.001), abnormal chest-X ray (p < 0.001), ICU admission (p = 0.015), and serum CRP (p < 0.001). In conclusion, following guidelines and the availability of rapid and reliable viral diagnostic methods dramatically reduces the unnecessary use of antibiotics in infants with severe bronchiolitis.

Sergio Cobo Durán y Víctor Hernández-Santaolalla (coords.) Madrid, Errata Naturae, 2013 360 páginas

AimsVaccine response is poor among children living with HIV. The gut microbiota has been identified as a potential target to improve vaccine immunogenicity, but data are scarce in the context of HIV infection.MethodsPilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected children were randomized to receive a mixture of symbiotics, omega-3/6 fatty acids, and amino acids or placebo for 4 weeks, each in combination with ART, and were then immunized against influenza. Vaccine response and safety of the nutritional supplementation were the primary outcomes.ResultsEighteen HIV-infected children completed the follow-up period (mean age 11.5 ± 4.14 years, 61% female). The nutritional supplement was safe but did not enhance the response to the influenza vaccine. A 4-fold rise in antibody titers was obtained in only 37.5% of participants in the intervention arm vs. 40% in the placebo. No immunological or inflammatory predictors of vaccine response were identified.ConclusionsIn this exploratory study, a 4-week course of symbiotics did not increase influenza vaccine immunogenicity in HIV-infected children. Larger studies are warranted to address the potential of modulating the microbiome in children living with HIV.

Millions of SARS-CoV-2 whole genome sequences have been generated to date. However, good quality data and adequate surveillance systems are required to contribute to meaningful surveillance in public health. In this context, the network of Spanish laboratories for coronavirus (RELECOV) was created with the main goal of promoting actions to speed up the detection, analyses, and evaluation of SARS-CoV-2 at a national level, partially structured and financed by an ECDC-HERA-Incubator action (ECDC/GRANT/2021/024). A SARS-CoV-2 sequencing quality control assessment (QCA) was developed to evaluate the network’s technical capacity. QCA full panel results showed a lower hit rate for lineage assignment compared to that obtained for variants. Genomic data comprising 48,578 viral genomes were studied and evaluated to monitor SARS-CoV-2. The developed network actions showed a 36% increase in sharing viral sequences. In addition, analysis of lineage/sublineage-defining mutations to track the virus showed characteristic mutation profiles for the Delta and Omicron variants. Further, phylogenetic analyses strongly correlated with different variant clusters, obtaining a robust reference tree. The RELECOV network has made it possible to improve and enhance the genomic surveillance of SARS-CoV-2 in Spain. It has provided and evaluated genomic tools for viral genome monitoring and characterization that make it possible to increase knowledge efficiently and quickly, promoting the genomic surveillance of SARS-CoV-2 in Spain.

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks’ gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants’ birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.

Abstract Background COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. Methods/design The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. Discussion This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. Trial registration ClinicalTrials.gov NCT04345523 . Registered on 30 March, 2020. First posted date: April 14, 2020.

We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed.

En este trabajo hemos analizado un corpus constituido por 100 pliegos sueltos. Nuestro objetivo es determinar si la calificación de conservadurismo con la que se caracteriza generalmente a la literatura de cordel española puede ser matizada a la luz de otras interpretaciones historiográficas, que conceden a la prensa popular la condición de radical. Hemos realizado un análisis de contenido en el que hemos localizado elementos propios del anticlericalismo o del discurso irreligioso, por un lado, y de la proclamación de una moral sexual relajada, por otro. Nuestra conclusión es que en la literatura de cordel puede documentarse la aspiración a hacer visibles otros modelos de comportamiento religioso y sexual, lo que permite hablar de un cierto grado de radicalismo ideológico.

Respiratory diseases such as bronchiolitis, and those with wheezing episodes, are highly important during infancy due to their potential chronicity. Immune response dysregulation is critical in perpetuating lung damage. Epigenetic modifications including microRNA (miRNA) post-transcriptional regulation are among the factors involved in alleviating inflammation. We evaluated the expression of miR-146a-5p, a previously described negative regulator of immunity, in infants with respiratory diseases, in order to study epigenetic regulation of the immune response. Nasopharyngeal aspirate (NPA) was obtained from infants with bronchiolitis (ongoing and post-disease) or with wheezing episodes in addition to healthy controls. Virus presence was determined by nested PCR, while miRNA and gene expression were studied in cells from NPAs using qPCR. Healthy small airway epithelial cells (SAECs) were used as an in vitro model. We observe a reduction in miR-146a-5p expression in infants with either of the two diseases compared to controls, suggesting the potential of this miRNA as a disease biomarker. Post-bronchiolitis, miR-146a-5p expression increases, though without reaching levels of healthy controls. MiR-146a-5p expression correlates inversely with the immune-related gene PTGS2, while its expression correlates directly with TSLP. When heathy donor SAECs are stimulated by poly:IC, we observe an increase in miR-146a-5p, with wounds having a synergistic effect. In conclusion, infants with respiratory diseases present reduced miR-146a-5p expression, possibly affecting immune dysregulation.

ABSTRACTDespite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT–PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.

The connection between Andalusia and Spanish chapbooks goes beyond the clear interest of the Spanish public of the eighteenth and nineteenth centuries in broadsides about bandits and gypsies, stories that perpetuated the topics of this region. An analysis of specialized production in this publishing genre demonstrates the leading role of Andalusia in the development of these publications. Indeed some of the printers and authors of most impact in those centuries were born in Cordoba, Cadiz or Seville. This study sketches the biographies and catalogues of these professionals of popular literature not only with the aim of offering relevant data on the publishing market in the south of Spain, but also to know the most popular titles in this product for mass consumption in Spain at that time.

Background and objective Very low birthweight (VLBW) infants are highly susceptible to respiratory infections. Information about prevalence of viral respiratory infections (VRIs) in neonatal intensive care unit (NICU) is scarce. Recent evidence suggests short-term and long-term impact of VRI in morbidity of VLBW infants. The goal of this study is to conduct a VRI surveillance in VLBW infants during NICU admission to address the prevalence, type of viruses and associated clinical features.Methods Prospective observational cohort study on infants below 32 gestational weeks admitted to a tertiary NICU during a 2-year period. Respiratory virus detection (influenza, parainfluenza, rhinovirus (hRV), enterovirus, respiratory syncytial virus, metapneumovirus, coronavirus, bocavirus and adenovirus) was performed by real time multiplex PCR assays in nasopharyngeal aspirates (NPAs), within the first 72 hours after birth and weekly, until discharge. Additional samples were taken if clinically indicated.Results 147 out of 224 eligible infants were enrolled. At least one positive NPA was found in 38% of the study cohort. Main viruses identified were hRV (58%) and adenovirus (31%). Among the 56 infants with positive NPA, 26 showed non-specific respiratory features in 58% (increased respiratory workload, tachypnoea, apnoea) or typical cold features in 38% (rhinorrhea, cough, fever), at least in one episode. Antibiotics were prescribed in 29% of cases. Positive infants showed higher rates of bronchopulmonary dysplasia (BPD), need for supplemental oxygen and mechanical ventilation, and had longer hospital stay. Cox regression analysis found BPD as an independent risk factor for viral infection (p

Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances for two of the three studied bat species (P. pygmaeus and P.kuhlii). These results increase our knowledge about the transmission mechanisms of adenoviruses.

Background: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied. Methods: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses’ polymerase chain reaction were collected monthly, and between visits in case of symptoms. Results: Twenty-two individuals were included (11 patients; 11 controls); 164 samples were obtained (81 patients; 84 controls). Patients presented respiratory symptoms more frequently compared with controls (26.5% vs. 3.5%; p < 0.01). Viral detection was observed in 23 (27.3%) episodes in patients and in 15 (17.8%) episodes in controls (p = 0.1). Rhinovirus was the most frequent virus in patients and controls (60% and 53.3%, respectively). Episodes with positive viral detection had associated symptoms in 54% of patients and 18% of controls (p = 0.07). However, patients with A-T presented a similar rate of symptoms during episodes with positive and negative viral detection (26% vs. 27%). The median points given for each questionnaire during symptomatic episodes with negative viral detection were 13/23 points, and during symptomatic positive detection, 7.5/23 points (p = 0.1). In the control group, all but two were asymptomatic during positive viral episodes (score: 2/23 and 3/23 points). Symptomatic episodes, with either positive or negative viral detection, were associated with lower IgA and higher IgM titers and higher CD8+ counts (p < 0.05), particularly when these episodes were moderate/severe. Conclusions: Patients with A-T more frequently present symptomatic viral infections than controls, especially those with lower IgA and higher IgM titers and higher CD8+ counts.

The figure of the generous bandit has remained for centuries in the popular collective imagination, but it will be Diego Corrientes (1757-1781) that did not commit any crime of blood, who best embodies this myth. Faced with the violent chapbooks about natural born killers as Francisco Esteban or Pigetas, the popularity of this character was a turning point in the telling of these stories, where the legend seems to win the battle to reality. The stories of arrogant criminals gave way to the social dramas of heroes with a impeccable moral, who are doomed to a life outside the law as victims of the injustices they have had to confront. This new model will prevail in the popular literature of the last bandits as Pernales (1879-1907), despite his infamous life.

Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets. R6 showed faster replication and pathogenicity than R7 in vitro and in mice. Subsequently, R6 was selected for the fitness comparison with the F strain in ferrets. Ferrets infected with the F virus showed more severe clinical signs, histopathological lung lesions, and viral quantification when compared to OR R6-infected animals. More importantly, differential viral kinetics correlated with differential pro-inflammatory host immune responses in the lungs of infected ferrets, where OR-infected animals developed a protective higher expression of type I IFN and Retinoid acid Inducible Gene I (RIG-I) genes early after infection, resulting in the development of milder disease. These results suggest the presence of early specific viral-host immune interactions relevant in the development of influenza-associated lung pathology.

Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses. Looking for potential virulence factors, we have identified a polymerase PA D529N mutation detected in a fatal IAV case, whose introduction into two different recombinant virus backbones, led to reduced defective viral genomes (DVGs) production. This mutation conferred low induction of antiviral response in infected cells and increased pathogenesis in mice. To analyze the association between low DVGs production and pathogenesis in humans, we performed a genomic analysis of viruses isolated from a cohort of previously healthy individuals who suffered highly severe IAV infection requiring admission to Intensive Care Unit and patients with fatal outcome who additionally showed underlying medical conditions. These viruses were compared with those isolated from a cohort of mild IAV patients. Viruses with fewer DVGs accumulation were observed in patients with highly severe/fatal outcome than in those with mild disease, suggesting that low DVGs abundance constitutes a new virulence pathogenic marker in humans.

Several amino acid changes have been previously implicated in adaptation of avian influenza viruses to human hosts, among them the D701N change in the PB2 polymerase subunit that also is the main determinant of avian virus pathogenesis in animal models. However, previous studies using recombinant viruses did not provide conclusive information of the contribution of this PB2 residue to pathogenicity in human influenza virus strains. We identified this mutation in an A(H1N1)pdm09-like human influenza virus isolated from an infected patient with pneumonia and acute respiratory failure, admitted to the intensive care unit. An exhaustive search has revealed PB2-D701 as a highly conserved position in all available H1N1 human virus sequences in NCBI database, showing a very low prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with severe or fatal outcome in those scarce cases with known disease outcome of the infection. In these patients, the residue PB2-701N may contribute to pathogenicity as it was previously reported in humans infected with avian viruses. This study helps to clarify a debate that has arisen regarding the role of PB2-D701N in human influenza virus pathogenicity.

Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections.Our aim was to compare the frequency of asthma development at 6-8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection.A cross-sectional study was performed in 244 children currently aged 6-8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction) and clinical data were prospectively taken during admission for bronchiolitis.Median current age at follow-up was 7.3 years (IQR: 6.7-8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented "wheezing in the last 12 months", data that strongly correlate with current prevalence of asthma. "Dry cough at night" was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6-8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317, p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p

BACKGROUND:Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. METHODS AND FINDINGS:A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children's mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p

Objetivos: Describir la prevalencia de síndrome gripal en el invierno de 2009 y los factores asociados a su ocurrencia. Método: Estudio transversal en 18 hospitales españoles. Los voluntarios respondieron un cuestionario de salud, informando sobre si habían sufrido síndrome gripal y su estado vacunal. Resultados: Participaron 1289 trabajadores sanitarios, y de ellos, 72 (5,6%) refirieron gripe en su familia, 195 (15,1%) se vacunaron frente al virus A/California/7/2009/H1N1 y 75 (5,8%, intervalo de confianza del 95% [IC95%]: 4,5-7,1) sufrieron síndrome gripal. Hubo diferencias entre comunidades autónomas. En el análisis de regresión logística, se asoció a síndrome gripal trabajar en la Comunidad de Madrid (odds ratio [OR]=8,31, IC95%: 1.05-65.39), tener casos de gripe en la familia (OR=2,84, IC95%: 1,41-5,73) y no estar vacunado frente a la gripe A (OR=2,68, IC95%: 1,05-6,82). Conclusiones: La presencia de casos en la familia y la comunidad donde se trabaja determinaron una diferente prevalencia de síndrome gripal. La vacuna se asoció a una menor prevalencia de la enfermedad.Objectives: To describe the prevalence of influenza-like syndrome in winter 2009 and the factors associated with its occurrence. Methods: A cross-sectional study was carried out in 18 hospitals in Spain. Volunteers completed a health questionnaire in which they reported the occurrence of influenza-like syndrome and vaccination and demographic status. Results: A total of 1,289 healthcare workers participated. Of these, 72 (5.6%) reported influenza in their family, 195 (15.1%) had been vaccinated against the A/California/7/2009/H1N1 virus and 75 (5.8%, 95%CI: 4.5-7.1%) had been diagnosed with influenza like-syndrome. There were differences among regions. In logistic regression analysis, the following factors were associated with a higher prevalence of influenza-like syndrome: working in Madrid (OR=8.31, 95%CI: 1.05-65.39), the occurrence of cases of influenza in the family (OR=2.84, 95%CI: 1.41-5.73) and not having been vaccinated against influenza A (H1N1) (OR=2.68, 95% CI: 1.05-6.82). Conclusions: Differences in the prevalence of influenza-like syndrome were due to the occurrence of familiar cases and region. Vaccination against influenza A (H1N1) was associated with a lower prevalence of the disease.

A thorough search for bat herpesviruses was carried out in oropharyngeal samples taken from most of the bat species present in the Iberian Peninsula from the Vespertilionidae, Miniopteridae, Molossidae and Rhinolophidae families, in addition to a colony of captive fruit bats from the Pteropodidae family. By using two degenerate consensus PCR methods targeting two conserved genes, distinct and previously unrecognized bat-hosted herpesviruses were identified for the most of the tested species. All together a total of 42 potentially novel bat herpesviruses were partially characterized. Thirty-two of them were tentatively assigned to the Betaherpesvirinae subfamily while the remaining 10 were allocated into the Gammaherpesvirinae subfamily. Significant diversity was observed among the novel sequences when compared with type herpesvirus species of the ICTV-approved genera. The inferred phylogenetic relationships showed that most of the betaherpesviruses sequences fell into a well-supported unique monophyletic clade and support the recognition of a new betaherpesvirus genus. This clade is subdivided into three major clades, corresponding to the families of bats studied. This supports the hypothesis of a species-specific parallel evolution process between the potentially new betaherpesviruses and their bat hosts. Interestingly, two of the betaherpesviruses' sequences detected in rhinolophid bats clustered together apart from the rest, closely related to viruses that belong to the Roseolovirus genus. This suggests a putative third roseolo lineage. On the contrary, no phylogenetic structure was detected among several potentially novel bat-hosted gammaherpesviruses found in the study. Remarkably, all of the possible novel bat herpesviruses described in this study are linked to a unique bat species.

Introduction: The Spanish influenza surveillance system (SISS) maintained its activity during the summer of 2009 to monitor the influenza pandemic. Objectives: To describe pandemic influenza activity from May to September 2009 and to estimate the effectiveness of the 2008-9 seasonal influenza vaccine against laboratory-confirmed pandemic (H1N1) 2009 influenza. Methods: Data from the SISS were used to identify the trend of pandemic (H1N1) 2009 influenza outside the influenza season. For the effectiveness study, we compared the vaccination status of notified cases [influenza-like illnesses (ILI) laboratory confirmed as pandemic influenza] with that of the test-negative controls. Results: The first laboratory-confirmed case of the pandemic virus was notified in the system in week 20/2009. The ILI rate increased gradually in the study period, exceeding basic activity in week 38. The proportion of pandemic (H1N1) 2009 influenza viruses detected by the system represented 14% in week 20/2009 and rapidly increased to 90% in week 34. The adjusted vaccine effectiveness of the 2008-9 seasonal vaccine against laboratory-confirmed pandemic influenza was 12% (-30; 41). Conclusions: The SISS became an essential tool for pandemic monitoring in Spain. The improved SISS will provide more accurate information on influenza activity in future seasonal or pandemic waves. Using surveillance data, we could not demonstrate the effectiveness of the seasonal 2008-9 vaccine against laboratory-confirmed pandemic influenza.Introducción: El Sistema de Vigilancia de Gripe en España (SVGE) continuó y reforzó su actividad durante el verano de 2009 con el objetivo de vigilar la evolución de la pandemia en España. Objetivos: Describir la actividad de la gripe pandémica en España de mayo a septiembre de 2009 y estimar la efectividad de la vacuna antigripal estacional 2008-2009 frente a casos confirmados de gripe pandémica (H1N1) 2009. Métodos: Se utilizaron datos del SVGE para presentar la evolución de la pandemia por virus (H1N1) 2009 fuera de la temporada de vigilancia 2008-2009. Para el estudio de la efectividad vacunal se comparó el estado vacunal de los casos de gripe pandémica confirmados por laboratorio con el de los casos negativos para el virus de la gripe (controles negativos). Resultados: El primer caso confirmado de virus pandémico se notificó en la semana 20/2009. La incidencia de gripe aumentó paulatinamente durante el periodo estudiado y sobrepasó el umbral basal en la semana 38/2009. La proporción de virus (H1N1) 2009 detectada por el SVGE fue del 14% en la semana 20 y aumentó rápidamente, llegando a alcanzar el 90% en la semana 34. La efectividad ajustada de la vacuna antigripal 2008-2009 frente a casos confirmados de gripe pandémica fue del 12% (-30; 41). Conclusiones: El SVGE se adaptó y mejoró de forma rápida a las exigencias nacionales e internacionales de vigilancia de la pandemia. Esta mejora supone información más precisa y de calidad en futuras ondas epidémicas/pandémicas. Con los datos obtenidos en vigilancia no se pudo demostrar alguna efectividad de la vacuna antigripal 2008-2009 frente a los casos de gripe pandémica confirmados por laboratorio.

Fundamento: La proporción de individuos asintomáticos que se infectan por gripe AH1N1v varía según las series. Los sanitarios están expuestos al virus de la gripe AH1N1v por su condición laboral, por lo que cabe esperar una prevalencia elevada de individuos con serología positiva sin presentar cuadro clínico asociado. El objetivo del estudio fue determinar la prevalencia de sanitarios asintomáticos con serología positiva para el virus de la gripe AH1N1v. Métodos: Se propuso un estudio prospectivo de cohortes en personal hospitalario en función de un hipotético gradiente decreciente de exposición al virus: personal de urgencias, área médica, área quirúrgica y celadores no de urgencias. Se extrajo sangre de los participantes en septiembre- octubre de 2009, noviembre-diciembre de 2009 y en abril-mayo de 2010, junto con la extracción se rellenaba un cuestionario de salud. Se ofreció la participación voluntaria a los miembros de los diferentes servicios. En sangre se procedió a determinar anticuerpos específicos frente al virus de la gripe AH1N1v por medio de inhibición de la hemaglutinación. Participaron 18 hospitales con un total de 1.371 participantes. Resultados: Se dispone de cuestionario de salud y de resultados serológicos de cuatro hospitales. Se observó una proporción variable de sanitarios asintomáticos con serología positiva sin haber sido vacunados (entre el 5,6! y el 83!). Sólo se vacunaron un 19,4! de los sanitarios, con un porcentaje de serologías positivas también variable (entre un 18,8! y 64,7!). El porcentaje de serologías positivas fue significativamente menor entre los celadores y el resto de categorías profesionales. La vacunación fue mayor entre los médicos que en el resto de estamentos profesionales. Conclusiones: Existe un porcentaje variable de individuos con serología positiva sin haber sufrido síntomas, con claras diferencias geográficas. Se observan también diferencias en la efectividad vacunal en términos serológicos.

In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.

Existen tres tipos de virus de la gripe: A, B y C. Estos virus evolucionan constantemente debido a que presentan dos características principales, la primera es la falta de capacidad correctora de la polimerasa viral que hace que se acumulen mutaciones puntuales en sus genes (deriva antigénica), y la segunda la naturaleza de su genoma formando por ocho segmentos lo que le permite el intercambio de genes entre distintos virus (salto antigénico). Esta plasticidad viral ha permitido que los virus de la gripe A sean capaces de adaptarse a diferentes hospedadores y adquirir capacidades pandémicas. El sistema de vigilancia de la gripe en España (SVGE) surgió como respuesta a la preocupación de que se produjera una pandemia, máxime después de los casos de gripe aviar detectados en el ser humano. Este sistema de vigilancia esta formado por dieciséis redes de médicos generales y pediatras centinela y diecinueve servicios de epidemiología, coordinados por el Centro Nacional de Epidemiología (CNE) y una red de dieciocho laboratorios, la red de laboratorios de Españoles de Gripe (ReLEG), coordinados por el Centro Nacional de Microbiología (CNM). El objetivo de este artículo es presentar la actuación de la ReLEG durante la pandemia producida por el virus de la gripe (H1N1)2009, durante la temporada 2009-2010. La función principal de la red es la vigilancia de los virus circulantes mediante su detección y posterior caracterización genética y antigénica, incluyendo la detección de las mutaciones de resistencia que afectan a los fármacos en uso, principalmente el Oseltamivir.

Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years.

Human adenovirus (HAdV) cause upper and lower respiratory tract infections. However, there are few large prospective studies focused on HAdVs acute infections requiring hospitalization. From 2005 to 2013 a prospective study was conducted on children admitted with acute respiratory infections. Specimens of nasopharyngeal aspirate were taken for virological study by PCR and clinical data was recorded. HAdV specimens were genotyped. Frequency and clinical course of HAdV infections were compared with RSV, rhinovirus (RV), human bocavirus (HBoV) and influenza in the same population. HAdV was detected in 403 cases of 2371 confirmed viral infections (17.2%) , of which 154 were single virus infections (38%). We genotyped 154 HAdVs. The most frequent genotypes were HAdV-3 (24%), HAdV-6 (21%), and HAdV-5 (20%). A total of 262 children had fever (64.9%); 194 suffered hypoxia (48%), and 147 presented infiltrate in chest x-rays (36.4%). The most frequent diagnoses were recurrent wheezing or asthma (51.7%), bronchiolitis (18.3 %), and pneumonia (11.9%), and 46 (11.4%) episodes required prolonged hospitalization (>7 days) due to the severity. Adenovirus single infections were compared with single infections of 598 RSV, 494 RV, 83 influenza and 78 HBoV. Significant clinical differences were found between HAdV, RSV and RV infections.

Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples.

Echovirus 13 (EV13), considered rare, was reported worldwide in 2000, mostly related to aseptic meningitis outbreaks. In Spain, 135 EV13 isolates were identified. The genetic relationships between 64 representative strains from Spain and other reported isolates from the United States, Germany, Italy, Japan, and Sweden were described by analyzing the partial sequence of the major capsid protein (VP1) gene. The strains from Spain were clearly identified as EV13 (79.5% similarity with the EV13 reference strain) and were grouped phylogenetically into two different clusters (by origination on either the Iberian Peninsula or Canary Islands). Isolates from Germany from 2000 clustered with the Canary Islands group. The isolates from other countries obtained before 2000 were genetically distant. Changes in EV13 coding sequence involved several differences in the C-terminal extreme of the VP1 protein. Part of the neutralizing antigenic site III has been described in this genome region in poliovirus and swine vesicular disease virus.

To assess whether infants hospitalized after an apparently life-threatening event had an associated respiratory virus infection, we analyzed nasopharyngeal aspirates from 16 patients. Nine of 11 infants with positive virus results were infected by rhinoviruses. We detected the new genogroup of rhinovirus C in 6 aspirates.

BACKGROUND: The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. OBJECTIVE: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. RESULTS: The 2008-09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010-11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). CONCLUSION: This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases.

Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).

The freedom of the press achieved after the Glorious Revolution was a context that was favorable for the appearance of a multitude of publications of all kinds, among which newspapers and magazines that propagated ideas in favor of gender equality stand out. This was a key moment for those working towards female emancipation, and they counted on the press as a great ally to spread their proposals in favor of the educational and labor regeneration of women. Likewise, there were the right circumstances for a series of feminist writers such as Rosa Marina, María Josefa Zapata, Margarita Pérez de Celis o Modesta Periú to deal with other issues, beyond the superficial theme of the headers dedicated at that time to their sex. This article collects some fragments of the works and publications in which these authors wrote or in which they were mentioned with the aim of using this source as a testimony of their biographies, as yet scarcely addressed.