Biomarkers of peanut allergy in children over time.

BACKGROUND: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. METHODS: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point. RESULTS: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time. CONCLUSIONS: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time.

Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

EAACI guidelines on the management of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes.

Serologic measurements for peanut allergy: Predicting clinical severity is complex.

Allergist-immunologists use serologic peanut allergy testing to maximize test sensitivity and specificity while minimizing cost and inconvenience. Recent advances toward this goal include a better understanding of specific IgE (sIgE) and component testing, epitope-sIgE assays, and basophil activation testing. Predicting reaction severity with serologic testing is challenged by a range of co-factors that influence reaction severity, such as the amount and form of any allergen consumed and comorbid disease. In 2020, the Allergy Immunology Joint Task Force on Practice Parameters recommended Ara h 2-sIgE as the most cost-effective diagnostic test for peanut allergy because of its superior performance, when compared with skin prick testing and serum IgE. Basophil activation testing, a functional test of allergic response not evaluated in the Joint Task Force on Practice Parameters guideline, is a promising option for both allergy diagnosis and prognosis. Similarly, epitope-sIgE testing may improve prediction of reaction thresholds, but further validation is needed. Despite advances in food allergy testing, many of these tools remain limited by cost, accessibility, and feasibility. In addition, there is a need for further research on how atopic dermatitis may be modifying serologic food allergy severity assessments. Given these limitations, allergy test selection requires a shared decision-making approach so that a patient's values and preferences regarding financial impact, inconvenience, and psychological effects are considered in the context of clinician expertise on the timing and use of optimized testing.

Skin as the target for allergy prevention and treatment.

The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a TH2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, such as the gut, may be crucial for lowering the risk and preventing atopic diseases, particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in patients with atopic dermatitis, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1, and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and topical calcineurin inhibitors, along with pioneering trials proposed to change their current use (Prevention of Allergy via Cutaneous Intervention and Stopping Eczema and ALlergy). We provide an overview of the novel therapies that enhance the skin barrier, such as probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and interleukin and janus kinases inhibitors. Last, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy and the experimental use of single-dose of adeno-associated virus vector gene immunotherapy.

Management of IgE-mediated food allergy in the 21st century.

The 21st century has seen the propulsion of research in the field of food allergy, which has driven real changes in the clinical approach. Allergen immunotherapy has been recommended for the active management of food allergy. Data have shown promising additional methods of treatment, including biologics. Efforts have been devoted to the risk stratification of food allergy and the standardization of the assessment of food-allergic severity. Alternative routes of administration of epinephrine are under investigation to minimize any mechanical issue and the fear of injections. Evidence-based guidelines have been published by the main international societies in the field of anaphylaxis and food allergy management and new updates are in preparation. In the coming years, treatment options that are currently in pre-clinical or early clinical evaluation will hopefully lead to safe and effective disease-modifying therapies for food allergy in clinical practice. The identification of reliable biomarkers and the standardization of definitions and measurement approaches, alongside a shared decision-making with patients and families, will be key for the development of personalized care and to help minimize the substantial burden of food allergy.

The future of food allergy: Challenging existing paradigms of clinical practice.

The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the-often complex-diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI Position Paper.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately 4 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

Early intervention and prevention of allergic diseases.

Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of (1) an intact epidermal barrier to prevent epicutaneous antigen presentation, (2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and (3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

Development and validation of combined symptom-medication scores for allergic rhinitis.

BACKGROUND: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. METHODS: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). RESULTS: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). CONCLUSION: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

Associations between child filaggrin mutations and maternal diet with the development of allergic diseases in children.

BACKGROUND: Filaggrin (FLG) loss-of-function mutations in children and maternal diet in pregnancy have been implicated in child allergy outcomes. This paper studies the questions: "do FLG mutations modify the effect of maternal diet on the odds of development of allergic diseases?" and "which factor leads to the highest rate of diagnosis allergic diseases over time, maternal diet, or FLG mutations?". METHODS: Exact logistic regressions studied effect modification. Cox proportional hazard models compared the rate of allergic disease development in three groups (N = 624): (1) children with FLG mutation, (2) children without FLG mutation whose mothers did not eat an allergy preventive diet, and (3) children without FLG mutation whose mothers ate an allergy preventive diet. Maternal diet was classified using a validated index. RESULTS: Cox models showed the development of atopic dermatitis, asthma, and wheeze was significantly higher for children in group 1 versus 3 (HR = 2.40 [1.32, 4.37], HR = 2.29 [1.05, 4.97], and HR 2.10 [1.004, 4.38], respectively), but not significantly higher for children in group 1 versus 2 (HR = 1.30 [0.74, 2.29], HR = 1.27 [0.61, 2.63], and HR = 1.29 [0.65, 2.58], respectively). Development of allergic rhinitis was significantly higher for group 1 versus 2 and 3 (1 vs. 2: HR = 2.29 [1.10, 4.76]; 1 vs. 3: HR = 3.21 [1.46, 7.08]). There was no significant effect modification for any outcome. CONCLUSION: Children with FLG mutation had similar risk of atopic dermatitis, asthma, and wheeze as children without an FLG mutation whose mothers did not eat an allergy preventive diet during pregnancy. Child FLG mutation did not modify the effect of maternal diet. The results suggest that maternal diet in pregnancy, a modifiable risk factor, could be a target for preventive interventions.

Allergic diseases and immunodeficiencies in children, lessons learnt from COVID-19 pandemic by 2022: A statement from the EAACI-section on pediatrics.

By the April 12, 2022, the COVID-19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short- and long-term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health-care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID-19 or dying from infection. Allergic diseases are not associated with a higher COVID-19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high-standard care. Although children faced a multitude of pandemic-related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence.

Food allergy across the globe.

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.

Early-life inhalant allergen exposure, filaggrin genotype, and the development of sensitization from infancy to adolescence.

BACKGROUND: We hypothesized that filaggrin (FLG) loss-of-function mutations modify the effect of allergen exposure on the development of allergic sensitization. OBJECTIVE: We sought to determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization and whether FLG mutations modulate these odds. METHODS: In a population-based birth cohort we measured mite, cat, and dog allergen levels in dust samples collected from homes within the first year of life. Sensitization was assessed at 6 time points between infancy and age 16 years. Genotyping was performed for 6 FLG mutations. RESULTS: In the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between FLG and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with FLG mutations compared with those without (odds ratio, 1.36; 95% CI, 1.02-1.80; P = .035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently greater among children with FLG mutations, but the interaction did not reach statistical significance. Different associations were observed for dogs: there was a significant interaction between FLG and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with FLG mutations who were exposed to a dog in infancy (odds ratio, 0.16; 95% CI, 0.03-0.86; P = .03). CONCLUSIONS: FLG loss-of-function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens.

Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study.

BACKGROUND: Peanut, tree nut, and sesame allergies are responsible for most life-threatening food-induced allergic reactions. Rates of coexistent allergy between these foods have been from mostly retrospective studies that include only a limited number of tree nuts or were not based on oral food challenges. OBJECTIVE: The Pronuts study is a multicenter European study (London, Geneva, and Valencia) assessing the challenge-proven rate of coexistent peanut, tree nut, and/or sesame seed allergy. METHODS: Children aged 0 to 16 years with at least 1 confirmed nut or sesame seed allergy underwent sequential diagnostic food challenges to all other nuts and sesame seed. RESULTS: Overall, the rate of coexistent peanut, tree nut, and sesame seed allergy was 60.7% (n = 74/122; 95% CI, 51.4% to 69.4%). Peanut allergy was more common in London, cashew and pistachio nut allergies were more common in Geneva, and walnut and pecan allergies were more common in Valencia. Strong correlations were found between cashew-pistachio, walnut-pecan, and walnut-pecan-hazelnut-macadamia clusters. Age (>36 months) and center (Valencia > Geneva > London) were associated with an increased odds of multiple nut allergies. By pursuing the diagnostic protocol to demonstrate tolerance to other nuts, participants were able to introduce a median of 9 nuts. CONCLUSION: We found a higher rate of coexistent nut and sesame seed allergies than previously reported. Performing sequential food challenges was labor intensive and could result in severe allergic reactions; however, it reduced dietary restrictions. Age was a significant predictor of multiple nut allergies, and thus the secondary spread of nut allergies occurred in older children.

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.

In-vivo diagnostic test allergens in Europe: A call to action and proposal for recovery plan-An EAACI position paper.

Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.

Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI).

With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.