Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

Aim and scopePediatric Allergy and Immunology publishes original contributions and comprehensive reviews related to the understanding and treatment of immune defi ciency, allergic infl ammatory and infectious diseases in children. Other areas of interest include development of specifi c and accessory immunity, and the immunological interaction during pregnancy and lactation between mother and child. As the journal is intended to promote communication between scientists engaged in basic research and clinicians working with children, both clinical and experimental work will be published.

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.

SummaryBackground In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. Objectives To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). Methods In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n = 16), SCIT (n = 16) or pharmacotherapy alone (n = 16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-g, IL-10, and TGF-b secretions were measured. Results SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (Po0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-b (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines.Conclusion Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.

Environmental exposure plays a major role in the development of allergic diseases.The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects.Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic

With this in mind, multiple vaccination strategies are currently pursued targeting the S protein as an ideal candidate protein that may elicit cross-protective immunity (Table 1). Additionally, as a therapeutic option, a broadly acting cocktail of repurposing drugs might be the most pragmatic strategy to combat COVID-19. 12 Drugs targeting the replication steps of the virus, 12 and therapeutics alleviating the observed cytokine storm and hyperinflammation reducing acute lung injury would help patients. Interestingly, off-label treatment with the IL-6 blocker tocilizumab has been described in Giamarellos-Bourboulis et al, 1 and several immunosuppressive drugs evaluated or approved for rheumatoid arthritis are currently assessed in clinical trials for COVID-19 patients.

The interaction of environmental and genetic factors with the immune system can lead to the development of allergic diseases. The essential step in this progress is the generation of allergen-specific CD4(+) T-helper (Th) type 2 cells that mediate several effector functions. The influence of Th2 cytokines leads to the production of allergen-specific IgE antibodies by B cells, development and recruitment of eosinophils, mucus production and bronchial hyperreactivity, as well as tissue homing of other Th2 cells and eosinophils. Meanwhile, Th1 cells may contribute to chronicity and the effector phases. T cells termed T regulatory (Treg) cells, which have immunosuppressive functions and cytokine profiles distinct from that of either Th1 or Th2 cells, have been intensely investigated during the last 13 years. Treg cell response is characterized by an abolished allergen-specific T cell proliferation and the suppressed secretion of Th1 and Th2-type cytokines. Treg cells are able to inhibit the development of allergen-specific Th2 and Th1 cell responses and therefore play an important role in a healthy immune response to allergens. In addition, Treg cells potently suppress IgE production and directly or indirectly suppress the activity of effector cells of allergic inflammation, such as eosinophils, basophils and mast cells. Currently, Treg cells represent an exciting area of research, where understanding the mechanisms of peripheral tolerance to allergens may soon lead to more rational and safer approaches for the prevention and cure of allergic diseases.