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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]

• 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]

• 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]

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]

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]

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]

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]