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Background: Current in vitro allergen‐specific IgE (sIgE) detection assays measure IgE against allergen extracts or molecules in a single‐ or multiplex approach. Direct comparisons of the performance of such assays among young children with common presentations of allergic diseases regardless of sensitization status are largely missing. Objectives: The aim of this study was a comparison of the analytical and diagnostic performance for common clinical questions of three commonly used technologies which rely upon different laboratory methodologies among children of the All Age Asthma (ALLIANCE) cohort (clinicaltrials.gov: NCT02496468). Methods: Sera from 106 paediatric study participants (mean age 4 years) were assessed for the presence of sIgE by means of the ImmunoCAP™ sx1 and fx5 mixes, the ImmunoCAP ISAC™ 112 microarray and a Euroline™ panel. Results: Total and negative concordance was high (>82%–>89%), while positive concordance varied considerably (0%–100%) but was also >50% for the most common sensitizations analysed (house dust mite and birch). All three test systems showed good sensitivity and specificity (AUC consistently > 0.7). However, no significant differences with regard to identifying sIgE sensitizations associated with symptoms in children with suspected pollen‐ or dust‐triggered wheeze or presenting with symptoms of allergic rhinoconjunctivitis or food allergy were detected. Extending the number of allergens did not change the similar performance of the three assay systems. Conclusion and Clinical Relevance: Among young children, the three sIgE assays showed good analytical and diagnostic concordance. Our results caution that the identification of larger numbers of sensitizations by more comprehensive multiplex approaches may not improve the clinical utility of sIgE testing in this age group. [ABSTRACT FROM AUTHOR]

Viral conjunctivitis is one of the most common disorders observed in ophthalmic emergency departments, yet no established treatment exists. Lately, antiviral medications have been introduced into clinical practice; however, a systematic review focusing on their use and effectiveness in the treatment of viral conjunctivitis has not been previously reported. We systemically reviewed the literature to identify studies where antiviral drugs were used to treat viral conjunctivitis. Currently, aciclovir, trifluridine and valaciclovir are commonly used as antiviral agents to treat herpesvirus infections. Cidofovir has been used successfully to treat some cases of adenoviral conjunctivitis, although toxicity has also been reported. The use of other medications, such as idoxuridine, has been minimized in clinical practice due to their high toxicity. Interestingly, most of the antiviral drugs developed are used to treat herpesvirus infections, while less progress has been made in the field of adenoviral infections. For other viral causes of conjunctivitis, no effective remedy is currently available, and treatment focuses on the relief of symptoms. Caution should be exercised when coadministering other pharmacological agents, such as corticosteroids, because of emerging adverse effects. [ABSTRACT FROM AUTHOR]

Background. Infection of the chorioamnion with Ureaplasma urealyticum has been associated with low birth weight. Respiratory tract colonization in preterm infants has been associated with the development of chronic lung disease (CLD). The purpose of the present study was to determine the frequency of colonization of the mother's vagina and the preterm infant's respiratory tract and to associate U. urealyticum with premature birth and with development of CLD in the newborn. Methods. The present prospective study involved 126 mothers with preterm delivery and 125 mothers with full-term delivery, as well as their offspring. Vaginal secretion specimens were obtained from each mother before delivery. Rhinopharyngeal secretion or tracheal lavage specimens were collected after the birth of each premature and full-term infant and then periodically during hospitalization. Results. Vaginal Ureaplasma colonization occurred among 3 6.5% of mothers with preterm delivery and among 38% of mothers with full-term delivery. The rate of vertical transmission was 33% and 17% for mothers with preterm delivery and mothers with full-term delivery, respectively. The transmission rate for infants, according to birth weight, was as follows: 60%, for infants with a birth weight of <1000 g; 50%, for infants with a birth weight of 1000-1500 g; and 15.3%, for infants with a birth weight of &ges;1500 g (P = .001). The median gestational age of preterm infants born to colonized mothers was 28.5 weeks, and that of preterm infants born to noncolonized mothers was 32 weeks (P< .0001). The median birth weight of colonized preterm infants was 1135 g, and that of noncolonized infants was 1670 g (P< .0001). Twenty-four percent of preterm infants and 10% of full-term infants were colonized with U. urealyticum. Of colonized preterm infants, 27% developed CLD, compared with 9% of noncolonized infants (P = .03). Mortality was significantly higher among colonized preterm infants (P = .003). Conclusions. The rate of vertical transmission is highest among preterm infants with a birth weight of <1500 g. Vaginal colonization with Ureaplasma organisms is associated with premature delivery. Colonization of the respiratory tract of infants is associated with the development of CLD and with increased mortality. [ABSTRACT FROM AUTHOR]

To cite this article: Skevaki CL, Maggina P, Santos AF, Alves RR, Antolin-Amerigo D, Borrego LM, Bretschneider I, Butiene I, Couto M, Fassio F, Gardner J, Xatzipsalti M, Hovhannisyan L, Hox V, Makrinioti H, O'Neil SE, Pala G, Rudenko M, Santucci A, Seys S, Sokolowska M, Whitaker P, Heffler E. The 10th anniversary of the Junior Members and Affiliates of the European Academy of Allergy and Clinical Immunology. Pediatric Allergy Immunology 2011: 22: 754-757. Abstract This year is the 10th anniversary of the European Academy of Allergy and Clinical Immunology (EAACI) Junior Members and Affiliates (JMAs). The aim of this review is to highlight the work and activities of EAACI JMAs. To this end, we have summarized all the initiatives taken by JMAs during the last 10 yr. EAACI JMAs are currently a group of over 2380 clinicians and scientists under the age of 35 yr, who support the continuous education of the Academy's younger members. For the past decade, JMAs enjoy a steadily increasing number of benefits such as free online access to the Academy's journals, the possibility to apply for Fellowships and the Mentorship Program, travel grants to attend scientific meetings, and many more. In addition, JMAs have been involved in task forces, cooperation schemes with other scientific bodies, organization of JMA focused sessions during EAACI meetings, and participation in the activities of EAACI communication platforms. EAACI JMA activities represent an ideal example of recruiting, training, and educating young scientists in order for them to thrive as future experts in their field. This model may serve as a prototype for other scientific communities, several of which have already adapted similar policies. [ABSTRACT FROM AUTHOR]

• Enterovirus/rhinovirus and human respiratory syncytial virus (HRSV) were the most prevalent respiratory viruses among children. • Subanalysis revealed differences in regional, seasonal, and age group distribution. • Highest prevalence was found in children up to 1 year old. • The prevalence of HRSV increased in the second half of the pandemic. This meta-analysis aimed to assess the prevalence of respiratory viruses among children under the special conditions of the COVID-19 pandemic. Five databases were systematically searched to assess the pooled prevalence of various respiratory viruses in different age groups, regions, seasons, and in patients with and without confirmed SARS-CoV-2 coinfection. Moreover, we looked at the virus distribution in the first and second half of the pandemic and countries with distinct economic status. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and the systematic review was registered on PROSPERO (CRD42022379297). Enterovirus/rhinovirus and human respiratory syncytial virus (HRSV) were the most prevalent pathogens among children. The prevalence of HRSV increased in the second half of the pandemic. The prevailing viruses vary according to the SARS-CoV-2-coinfection status, season, region, and country´s economic status. This meta-analysis shows the epidemiology of respiratory viruses other than SARS-CoV-2 in children aged 0 to 12 years during the COVID-19 pandemic. Because major events, such as a pandemic, can alter epidemiology patterns, it is important to know them to improve health education measures, develop vaccines and medicines for vulnerable groups, as a guide for prevention strategies, and help with clinical decisions. [ABSTRACT FROM AUTHOR]

The prevalence and complexity of allergic diseases have increased in recent decades, leading to a significant burden for patients and their families. However, training in Allergy and Clinical Immunology (ACI) varies worldwide, with significant heterogeneity between countries. This variability may limit the number of healthcare professionals and researchers undergoing ACI training in the future. To address this, the European Academy of Allergy and Clinical Immunology (EAACI) has developed a mentorship program to support young professionals in enhancing their skills and network. The program has been successful and may serve as a model for other scientific organizations in the ACI field. [Extracted from the article]

Introduction: The leukotriene pathway may be implicated in the induction of virus-induced inflammation. Respiratory epithelial cells may express low levels of 5-lipoxygenase (5-LO) and release leukotrienes (LTs) C4, D4, and E4, upon exposure to viruses or other stimuli. Enhanced expression of 5-LO pathway proteins after rhinovirus (RV) infection has previously been described. We hypothesized that anti-leukotriene treatment of epithelial cells, with or without exposure to RV-infected peripheral blood mononuclear cells (PBMCs)-conditioned media, may inhibit RV-induced up-regulation of inflammatory cytokines. Methods: PBMCs from a healthy donor were exposed to RV1B and supernatants were harvested at 48 h post infection. BEAS-2B cells were infected with RV, with or without conditioning with the PBMC supernatant. Treatment with anti-LT agents was performed either on both PBMCs and BEAS-2B or at the bronchial epithelial level only, with varying concentrations of montelukast (CysLT receptor antagonist) or MK-886 [FLAP(5-lipoxygenase-activating-protein) inhibitor]. Evaluation of the inflammatory cytokines IL-8, RANTES, IL-11, IL-6, and IP-10 was performed using ELISA. Results: Our results show that anti-LT treatment of RV-infected bronchial epithelial cells suppresses epithelial RV-mediated cytokine production, independent of conditioning. Conclusions: This observation may represent an indirect mode of action of the anti-leukotrienes in virus-induced asthma. [ABSTRACT FROM AUTHOR]

• Rhinovirus/Enterovirus were predominant respiratory viruses during COVID-19 pandemic. • Virus prevalence was higher in non-COVID patients than in those who were COVID-coinfected. • For some viruses, prevalence increased in the second half when restrictions eased. • Non-SARS-CoV-2 prevalence decreased in many studies compared with pre-pandemic times. • No age-specific distribution of the viruses could be identified except for human metapneumovirus. Since the beginning of the COVID-19 pandemic, efforts have been made to contain the spread of the virus. However, the epidemiological burden of other respiratory viruses during the pandemic is unclear. We aim to address the epidemiology of respiratory viruses on adults/adolescents since the beginning of the pandemic. We systematically searched five databases and performed a meta-analysis to explore the pooled prevalence of respiratory viruses in different geographical regions, age groups, and periods and compared the prevalence between COVID-19 cases and non-COVID-19 patients. Enteroviruses/rhinoviruses were highly prevalent compared to other viruses. Different viruses were dominant in different regions. No significant differences in prevalence were found between different age groups, except for human metapneumovirus. There was an increase in prevalence of non-SARS-CoV-2 viruses in the second half of the pandemic (July 2021-December 2022). Comparison of COVID-19 and non-COVID patients showed a higher prevalence in the non-COVID group, significant for influenza, seasonal coronaviruses, and human parainfluenza viruses. Our findings indicate that enteroviruses/rhinoviruses were less impacted by healthcare measures compared with other respiratory viruses. The relaxation of measures in the second half led to an increased pooled prevalence of infections. Several factors may explain the lower prevalence among individuals infected with COVID-19. [ABSTRACT FROM AUTHOR]

Respiratory virus infections play a major role in asthma, while there is a close correlation between asthma and food allergy. We hypothesized that T cell-mediated heterologous immunity may induce asthma symptoms among sensitized individuals and used two independent in silico pipelines for the identification of cross-reactive virus- and food allergen- derived T cell epitopes, considering individual peptide sequence similarity, MHC binding affinity and immunogenicity. We assessed the proteomes of human rhinovirus (RV1b), respiratory syncytial virus (RSVA2) and influenza-strains contained in the seasonal quadrivalent influenza vaccine 2019/2020 (QIV 2019/2020), as well as SARS-CoV-2 for human HLA alleles, in addition to more than 200 most common food allergen protein sequences. All resulting allergen-derived peptide candidates were subjected to an elaborate scoring system considering multiple criteria, including clinical relevance. In both bioinformatics approaches, we found that shortlisted peptide pairs that are potentially binding to MHC class II molecules scored up to 10 × lower compared to MHC class I candidate epitopes. For MHC class I food allergen epitopes, several potentially cross-reactive peptides from shrimp, kiwi, apple, soybean and chicken were identified. The shortlisted set of peptide pairs may be implicated in heterologous immune responses and translated to peptide immunization strategies with immunomodulatory properties. [ABSTRACT FROM AUTHOR]

Heat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress. [ABSTRACT FROM AUTHOR]

Since the onset of COVID-19, several assays have been deployed for the diagnosis of SARS-CoV-2. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first set of guidelines on SARS-CoV-2 in vitro diagnosis in February 2022. Because the COVID-19 landscape is rapidly evolving, the relevant ESCMID guidelines panel releases an update of the previously published recommendations on diagnostic testing for SARS-CoV-2. This update aims to delineate the best diagnostic approach for SARS-CoV-2 in different populations based on current evidence. An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. The panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the population, intervention, comparison, and outcome (PICO) format was developed at the beginning of the process. For each PICO, 2 panel members performed a literature search focusing on systematic reviews with a third panellist involved in case of inconsistent results. The panel reassessed the PICOs previously defined as priority in the first set of guidelines and decided to address 49 PICO questions, because 6 of them were discarded as outdated/non-clinically relevant. The 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)-adoption, adaptation, and de novo development of recommendations (ADOLOPMENT)' evidence-to-decision framework was used to produce the guidelines. After literature search, we updated 16 PICO questions; these PICOs address the use of antigen-based assays among symptomatic and asymptomatic patients with different ages, COVID-19 severity status or risk for severe COVID-19, time since the onset of symptoms/contact with an infectious case, and finally, types of biomaterials used. [ABSTRACT FROM AUTHOR]

The article discusses use of allergen‐specific immunotherapy (AIT) to cure allergic diseases by attacking their antigen‐specific immunologic mechanisms. Topics include better standardization of allergen products for diagnosis and therapy with molecular allergology, selection of molecules in order to identify genuine sensitization to the allergen, and producing recombinant molecules with hybrid technology.

Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies. The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings. MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern. Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union. Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age. Molecular and/or antigen-based SARS-CoV-2 POCTs. Laboratory-based SARS-CoV-2 RT-PCR. Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome. A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9–95.4%) and 97.6% (95% CI, 96.6–98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2–73.8%) and 98.9% (95% CI, 98.5–99.2%), respectively. Further studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples. [ABSTRACT FROM AUTHOR]

Background: After the re-introduction of ImmunoCAP® ISAC sIgE 112 on the market, we undertook a study to evaluate the performance of this multiplex-based immunoassay for IgE measurements to allergen components. Methods: The study was carried out at 22 European and one South African site. Microarrays from different batches, eight specific IgE (sIgE) positive, three sIgE negative serum samples and a calibration sample were sent to participating laboratories where assays were performed according to the manufacturer's instructions. Results: For both the negative and positive samples results were consistent between sites, with a very low frequency of false positive results (0.014%). A similar pattern of results for each of the samples was observed across the 23 sites. Homogeneity analysis of all measurements for each sample were well clustered, indicating good reproducibility; unsupervised hierarchical clustering and classification via random forests, showed clustering of identical samples independent of the assay site. Analysis of raw continuous data confirmed the good accuracy across the study sites; averaged standardized, site-specific ISU-E values fell close to the center of the distribution of measurements from all sites. After outlier filtering, variability across the whole study was estimated at 25.5%, with values of 22%, 27.1% and 22.4% for the 'Low', 'Moderate to High' and 'Very High' concentration categories, respectively. Conclusions: The study shows a robust performance of the ImmunoCAP® ISAC 112 immunoassay at different sites. Essentially the same results were obtained irrespective of assay site, laboratory-specific conditions and instruments, operator, or the use of microarrays from different batches. [ABSTRACT FROM AUTHOR]

Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs). To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations. We also describe the commonalities of the defective immune pathways across these susceptible populations that may represent possible targets for future therapeutic or preventative approaches. We conducted free searches in Medline, Scopus, and Google Scholar for studies focusing on potential mechanisms of immune dysfunction that may be associated with severe viral RTIs in susceptible populations with conditions including pregnancy, obesity, diabetes mellitus, hypertension, cardiovascular disease, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and extremes of age. We considered preclinical/animal data, original human studies, and reviews. Innate and adaptive immune responses become quantitatively and qualitatively compromised in aging, obesity, and diabetes mellitus, with the most pronounced changes affecting T cells. Moreover, immune dysregulation by the so-called inflamm-aging results in chronic low-grade inflammation in such conditions. Increased leptin levels affect the immune system particularly in obesity, while leptin dysregulation plays a role in asthma and COPD pathogenesis. Deficient production of interferon (IFN) type I and III in response to rhinovirus contributes to asthma exacerbations. Similar attenuation of IFN production in response to influenza and rhinovirus has been documented in pregnancy. Dampened type I IFN responses have also been found in diet-induced obese mice and in obese individuals. Immunosenescence and chronic low-grade inflammation accompanying aging and a variety of chronic conditions, such as diabetes, obesity, asthma, COPD, chronic renal disease, and hypertension, contribute to the poor outcomes observed following viral respiratory infections. Commonly affected pathways may represent potential future therapeutic targets. [ABSTRACT FROM AUTHOR]

The objective of these guidelines is to identify the most appropriate diagnostic test and/or diagnostic approach for SARS-CoV-2. The recommendations are intended to provide guidance to clinicians, clinical microbiologists, other health care personnel, and decision makers. An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search focusing on systematic reviews, with a third panellist involved in case of inconsistent results. Quality of evidence assessment was based on the GRADE-ADOLOPMENT (Grading of Recommendations Assessment, Development and Evaluation - adoption, adaptation, and de novo development of recommendations) approach. A total of 43 PICO questions were selected that involve the following types of populations: (a) patients with signs and symptoms of COVID-19; (b) travellers, healthcare workers, and other individuals at risk for exposure to SARS-CoV-2; (c) asymptomatic individuals, and (d) close contacts of patients infected with SARS-CoV-2. The type of diagnostic test (commercial rapid nucleic acid amplification tests and rapid antigen detection), biomaterial, time since onset of symptoms/contact with an infectious case, age, disease severity, and risk of developing severe disease are also taken into consideration. [ABSTRACT FROM AUTHOR]

Background: Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA.Methods: Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells.Results: NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1β mRNA was positively correlated with protein expression. Sputum IL-1β mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1β mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1β augmenting TGF-β1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors.Conclusions: IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways.Trial Registration: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406). [ABSTRACT FROM AUTHOR]

Although molecular tests are considered the reference standard for coronavirus disease 2019 (COVID-19) diagnostics, serological and immunological tests may be useful in specific settings. This review summarizes the underlying principles and performance of COVID-19 serological and immunological testing. Selected peer-reviewed publications on COVID-19 related serology and immunology published between December 2019 and March 2021. Serological tests are highly specific but heterogeneous in their sensitivity for the diagnosis of COVID-19. For certain indications, including delayed disease presentations, serological tests can have added value. The presence of antibodies against SARS-CoV-2 may indicate a recent or past COVID-19 infection. Lateral flow immunoassay (LFIA) antibody tests have the advantages of being easy and fast to perform, but many have a low sensitivity in acute settings. Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassays (CLIAs) have higher sensitivities. Besides humoral immunity, cellular immunity is also essential for successful host defences against viruses. Enzyme-linked immunospot (ELISpot) assays can be used to measure T-cell responses against SARS-CoV-2. The presence of cross-reactive SARS-CoV-2-specific T cells in never exposed patients suggests the possibility of cellular immunity induced by other circulating coronaviruses. T-cell responses against SARS-CoV-2 have also been detected in recovered COVID-19 patients with no detectable antibodies. Serological and immunological tests are primarily applied for population-based seroprevalence studies to evaluate the effectiveness of COVID-19 control measures and increase our understanding of the immunology behind COVID-19. Combining molecular diagnostics with serological tests may optimize the detection of COVID-19. As not all infected patients will develop antibodies against SARS-CoV-2, assessment of cellular immunity may provide complementary information on whether a patient has been previously infected with COVID-19. More studies are needed to understand the correlations of these serological and immunological parameters with protective immunity, taking into account the different circulating virus variants. [ABSTRACT FROM AUTHOR]

Though women increasingly make up the majority of medical-school and other science graduates, they remain a minority in academic biomedical settings, where they are less likely to hold leadership positions or be awarded research funding. A major factor is the career breaks that women disproportionately take to see to familial duties. They experience a related, but overlooked, hurdle upon their return: they are often too old to be eligible for 'early-career researcher' grants and 'career-development' awards, which are stepping stones to leadership positions in many institutions and which determine the demographics of their hierarchies for decades to come. Though age limits are imposed to protect young applicants from more experienced seniors, they have an unintended side effect of excluding returning workers, still disproportionately women, from the running. In this joint effort by the European Society of Clinical Microbiology and Infectious Diseases, the Federation of European Microbiological Societies, the Infectious Disease Society of America, the International Society for Infectious Diseases and the Swiss Society for Infectious Diseases, we invited all European Congress of Clinical Microbiology and Infectious Diseases-affiliated medical societies and funding bodies to participate in a survey on current 'early-career' application restrictions and measures taken to provide protections for career breaks. The following simple consensus recommendations are geared to funding bodies, academic societies and other organizations for the fair handling of eligibility for early-career awards: 1. Apply a professional, not physiological, age limit to applicants. 2. State clearly in the award announcement that career breaks will be factored into applicants' evaluations such that: • Time absent is time extended : for every full-time equivalent of career break taken, the same full-time equivalent will be extended to the professional age limit. • Opportunity costs will also be taken into account : people who take career breaks risk additional opportunity costs, with work that they did before the career break often being forgotten or poorly documented, particularly in bibliometric accounting. Although there is no standardized metric to measure additional opportunity costs, organizations should (a) keep in mind their existence when judging applicants' submissions, and (b) note clearly in the award announcement that opportunity costs of career breaks are also taken into account. 3. State clearly that further considerations can be undertaken, using more individualized criteria that are specific to the applicant population and the award in question. The working group welcomes feedback so that these recommendations can be improved and updated as needed. [ABSTRACT FROM AUTHOR]

Background: The measurement of specific IgE to allergenic extracts and molecules in patients with allergic rhinitis (AR) is crucial for a precise diagnosis and further immunotherapy. Companies providing in vitro diagnostic methods in allergology continuously strive for the optimization and modernization of such methods. A new generation of automated allergy tests based on chemiluminescence detection and paramagnetic microparticles is now available, with possible advantages in sample volume, cost‐effectiveness and avoidance of sample‐related interference. Objectives: To test whether sIgE antibody levels obtained with a new singleplex chemiluminescent method have a good agreement with the corresponding results obtained with a "gold standard" test. Methods: We tested sera from 368 AR patients. Specific IgE sera levels (kU/L) to a comprehensive panel of 15 allergen extracts and 6 molecules were tested with ImmunoCAP® (Thermo Fisher Scientific Inc, Phadia AB, Uppsala, Sweden) and NOVEOS™ (HYCOR® Biomedical, Garden Grove, CA, USA). We evaluated the qualitative and quantitative performance of the new NOVEOS system in matching the outcome of ImmunoCAP to each of the examined allergens. Results: In relation to ImmunoCAP, the overall diagnostic sensitivity and specificity of sIgE tests with NOVEOS were 90.8% (95% CI = 88.6–92.7) and 96.2% (95% CI = 93.9–97.8), respectively. These values were higher when only molecules were considered (sensitivity = 98.7% [95% CI = 96.4%–99.7%]; specificity = 94.2% [95% CI = 88.4%–97.6%]) and lower when only extracts were considered (sensitivity = 87.6% [95% CI = 84.7%–90.2%]; specificity = 97% [95% CI = 94.4%–98.6%]). Spearman's correlation between the data set of both methods for a ≥ 0.1 kU/L cut‐off was 0.84 (p <.001). Conclusions: The new singleplex NOVEOS system presented good results for qualitative and quantitative comparisons when testing specific serum IgE antibodies against a range of 21 allergens. This novel immunoassay system using only 4 µl of sample per test appears to be robust and reliable and can, therefore, be used as an aid in allergy diagnosis. [ABSTRACT FROM AUTHOR]

The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses. [ABSTRACT FROM AUTHOR]

Objectives: Detection of allergen-specific immunoglobulin E (sIgE) is important for the diagnosis of allergy. IgE sensitization is commonly demonstrated in vivo by skin prick testing (SPT), or in vitro utilizing automated systems. Recently, HYCOR® Biomedical launched its new system for allergen sIgE testing called the NOVEOS™ Immunoanalyzer. This study aims to evaluate the analytical performance of the NOVEOS system in a bi-center study at Philipps-University Marburg (Site-1) and Charité Medical University Berlin (Site-2), respectively. Methods: The analytical performance was evaluated based on the guidelines I/LA20-A3, EP5-A3, EP17-A2, EP6-A, EP7-A3, and EP9-A3 of the Clinical and Laboratory Standards Institute (CLSI). Results: The conducted repeatability and within-laboratory precision tests provided acceptable performance with 3.0%–11.9% coefficient of variation across both sites. The limit of blank (LoB) and limit of detection (LoD) were <0.1 kU/L at both centers. A within-parameter linearity for all tested allergens was reported at both sites. Of note, no significant interference was observed for high levels of biotin, methylprednisolone, diphenhydramine, omalizumab, or ranitidine. Method comparison between the NOVEOS calibration and the latest World Health Organization (WHO) reference standard showed good agreement at both sites. Conclusions: The results from the analytical performance of the NOVEOS allergen sIgE assay and instrument testing at both sites were comparable. Overall, a good precision and linearity as well as a detection limit <0.1 kU/L were observed, with minimal impact of common interfering substances on patient recoveries. The NOVEOS is calibrated to the latest WHO reference standard and adds benefits like a small sample size and para-magnetic microparticles that improve upon third-generation allergen sIgE assays' design and performance. [ABSTRACT FROM AUTHOR]

Keywords: airway epithelium; cryopreservation; human rhinovirus EN airway epithelium cryopreservation human rhinovirus 1486 1489 4 06/01/20 20200601 NES 200601 To the Editor, Human epithelial cell lines (eg, A549 and BEAS-2B cells), as well as primary nasal and bronchial epithelial cells, have been used extensively to explore the role of virus-host interactions in respiratory allergic diseases.[1] In vitro cell cultures of primary airway epithelial cells from patients are a key model for these studies. In RV-infected cells, 45 genes were differentially expressed (36 higher and 9 lower in fresh compared to cryopreserved cells) (Figure C, Table S2B). In the last decades, epithelial infection models have evolved from using cell lines[5] to submerged primary cells[6] to air-liquid interphase differentiated cells.[7] At the same time, utilization of cryopreserved cells or tissues has increased considerably. [Extracted from the article]

Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENTWhat is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role.What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL's ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary. [ABSTRACT FROM AUTHOR]

Preschool wheezing diagnosis and management-Survey of physicians' and caregivers' perspective The most frequent response (50.7%) points out response to treatment, while allergy tests were also very popular, having been chosen by 34.1%. This is the first survey exploring physicians' views on preschool wheeze, showing that wheezing itself and its association with future asthma remain a substantial challenge for most physicians. Furthermore, this study does not include a completely random sample of physicians, due to methodology used (email and social network), so only physicians familiar with the technology were able to participate. [Extracted from the article]

Current data indicate that the "bronchiolitis" diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor. Respiratory syncytial virus‐induced bronchiolitis and rhinovirus‐induced first wheezing episode are the main clusters of severe bronchiolitis in less than 2‐year‐old children. It is important to distinguish these overlapping patient groups since they differ clinically, pathophysiologically, and genetically and are likely to respond to different treatments. The first episode of severe bronchiolitis appears to be a critical event and an opportunity for designing secondary prevention strategies for asthma. [ABSTRACT FROM AUTHOR]

Immunization is highly effective in preventing infectious diseases and therefore an indispensable public health measure. Allergic patients deserve access to the same publicly recommended immunizations as non-allergic patients unless risks associated with vaccination outweigh the gains. Whereas the number of reported possible allergic reactions to vaccines is high, confirmed vaccine-triggered allergic reactions are rare. Anaphylaxis following vaccination is rare, affecting <1/100 000, but can occur in any patient. Some patient groups, notably those with a previous allergic reaction to a vaccine or its components, are at heightened risk of allergic reaction and require special precautions. Allergic reactions, however, may occur in patients without known risk factors and cannot be predicted by currently available tools. Unwarranted fear and uncertainty can result in incomplete vaccination coverage for children and adults with or without allergy. In addition to concerns about an allergic reaction to the vaccine itself, there is fear that routine childhood immunization may promote the development of allergic sensitization and disease. Thus, although there is no evidence that routine childhood immunization increases the risk of allergy development, such risks need to be discussed. [ABSTRACT FROM AUTHOR]

Autophagy is a lysosomal degradation process involved in the turnover of organelles or other cell constituents, in providing sources for energy production under starving conditions and in cell metabolism. A key protein in the macroautophagic machinery is the autophagy-related protein (Atg) 7. Constitutive deletion of Atg7 is lethal at birth. A conditional deletion of Atg7 in hepatocytes leads to hepatomegaly and in aged animals to liver tumors. With this study, we aim at analyzing the hepatomegaly development in more detail. The 3- to 4-fold enlargement of the liver takes place between days 25 and 35 after birth (P25-P35) and persists at least until P90. This is accompanied by a change in the expression of enzymes involved in the glycogen/glucose metabolism. While glycogen synthesis is inhibited, glucose is preferentially kept as glucose-6-phosphate inside the cells, inducing a swelling of the cells caused by hyperosmolarity. An increase of lipogenic enzymes suggests that glucose-6-phosphate is delivered to lipogenic pathways, which is supported by the occurrence of a steatosis around P30. The development of hepatomegaly is accompanied by a polyploidisation of hepatocytes, an enhanced expression of genes related to inflammatory processes and an infiltration of macrophages and granulocytes. Our data provide evidence that the attenuation of macroautophagy in hepatocytes leads to a glucose retention that causes cell swelling. The resulting hepatomegaly, which develops in a time interval of about 10 days, perturbs liver perfusion and induces an inflammatory reaction together with polyploidisation. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which end otheliumfunction is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction,whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 new lydiagnosed patients with A Lamyloidosis. The levels ofVWF: Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher thanthe upper levels of controls. There was nosignificant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers. [ABSTRACT FROM AUTHOR]

Basketball incorporates intense eccentric muscle activity that induces muscle microtrauma and an inflammatory response. This study investigated time-dependent inflammatory and performance responses during a weekly microcycle after a basketball match. Twenty elite-standard players underwent a trial that comprised a match followed by a 6-day simulated in-season microcycle. The trial was preceded by a control condition that did not have a match. Blood sampling and tests of maximal-intensity exercise performance and muscle damage occurred before each condition, immediately after the match and daily thereafter for 6 consecutive days. The match induced marked increases in heart rate, lactate, ammonia, glucose, non-esterified fatty acids and triglycerides. Performance deteriorated for 24–48 h after the match, whereas knee flexor and extensor soreness increased for 48 and 24 h post-match, respectively. Inflammatory (leukocytes, C-reactive protein, creatine kinase activity, adhesion molecules, cortisol, uric acid and cytokines) and oxidative stress (malondialdehyde, protein carbonyls, oxidised glutathione, antioxidant capacity, catalase and glutathione peroxidase) markers increased for ~24 h and subsided thereafter. Reduced glutathione declined for 24 h after exercise. These results suggest that a basketball match elicits moderate and relatively brief (~24–48 h) inflammatory responses, is associated with marked but short-lived performance deterioration, but is less stressful than other intermittent-type sports. [ABSTRACT FROM PUBLISHER]

Background. Lipodystrophy characterized by adipose tissue redistribution and lipid and glucose metabolism abnormalities, is common among HIV-infected adults and children on highly-active-antiretroviral-therapy (HAART). In a previous study of HIV-infected children, we did not detect insulin resistance, despite a high percentage of body fat redistribution abnormalities. Aim of the study. To investigate the non-traditional adipokines Retinol-binding-Protein-4 (RBP4), neutrophil-gelatinase-associated-lipocalin (NGAL), a-Fatty-Acid-Binding-Protein (a-FABP) and YKL-40 in HIV-infected children on highly-active-antiretroviral-therapy and evaluate their possible association to lipodystrophic changes or insulin resistance. Methods. Seventeen vertically HIV-infected children (mean age: 12.5 years, mean duration of HAART: 5.2 years) and 20 age- and BMI-matched controls were recruited. The HIV-children were re-evaluated after 12 months. RBP4, NGAL, a-FABP and YKL-40 were assessed at study entry and 12 months later and were correlated to body fat content and insulin resistance. Results. RBP4 values were similar at study entry and 12 months later in HIV-children and controls and showed no correlation to body fat or insulin resistance. NGAL was lower in HIV children at study entry but normalized after 12 months with no positive correlation to insulin resistance. a-FABP was positively correlated to body fat content, especially to trunk fat, both at initial evaluation and at follow-up in HIV children and, after prolonged highly-active-antiretroviral-therapy, it was also positively correlated to insulin resistance. Conclusions. This study is the first one to demonstrate that a-FABP could be a useful marker in unraveling central fat accumulation in HIV-infected children on highly-active-antiretroviral-therapy. Large prospective studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Correct identification of the culprit allergen is an essential part of diagnosis and treatment in immunoglobulin E (IgE)-mediated allergic diseases. In recent years, molecular biology has made important advances facilitating such identification and overcoming some of the drawbacks of natural allergen extracts, which consist of mixtures of various proteins that may be allergenic or not, specific for the allergen source or widely distributed (panallergens). New technologies offer the opportunity for a more accurate component-resolved diagnosis, of benefit especially to polysensitized allergic patients. The basic elements of molecular diagnostics with potential relevance to immunotherapy prescription are reviewed here, with a focus on Southern European sensitization patterns to pollen allergens. We propose a basic algorithm regarding component-resolved diagnostic work-up for pollen allergen-specific immunotherapy candidates in Southern Europe; this and similar algorithms can form the basis of improved patient management, conceptually a 'Component-Resolved Allergy Management'. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare, newly defined autoimmune clinical entity that presents with atypical clinical manifestations. Most patients with anti-N-methyl-D-aspartate receptor encephalitis develop a progressive illness from psychosis into a state of unresponsiveness, with catatonic features often associated with abnormal movements and autonomic instability. This is the first report of anti-N-methyl-D-aspartate receptor encephalitis in a Greek pediatric hospital.Case Presentation: An 11-year-old Greek girl presented with clinical manifestations of acute psychosis. The differential diagnosis included viral encephalitis. The presence of a tumor usually an ovarian teratoma, a common clinical finding in many patients, was excluded. Early diagnosis and prompt immunotherapy resulted in full recovery up to one year after the initial diagnosis.Conclusion: Acute psychosis is a rare psychiatric presentation in children, diagnosed only after possible organic syndromes that mimic acute psychosis are excluded, including anti-N-methyl-D-aspartate receptor receptor encephalitis. Pediatricians, neurologists and psychiatrists should consider this rare clinical syndrome, in order to make an early diagnosis and instigate appropriate treatment to maximize neurological recovery. [ABSTRACT FROM AUTHOR]

Background: Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods: Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry. Results: RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion: RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling. [ABSTRACT FROM AUTHOR]