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The natural history of COVID‐19 caused by SARS‐CoV‐2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi‐organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10‐15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose‐binding lectin). If SARS‐CoV‐2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high‐affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low‐moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID‐19 facilitates re‐inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies ("viral auto‐inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This "quantitative and time‐/sequence‐dependent" model has several implications for prevention, diagnosis, and therapy of COVID‐19 at all ages. [ABSTRACT FROM AUTHOR]

Background: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. Objective: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. Methods: Nasal secretions were collected with an absorbent device (Merocel 2000®, Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC‐112, TFS) were measured in NS and serum. Results: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. Conclusions: The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire. [ABSTRACT FROM AUTHOR]

Background Previous studies of serum total IgE (t-IgE) were not able to discriminate well-enough atopic from non-atopic subjects, that is, with or without serum-specific IgE antibodies to allergens. Objectives To model growth curves of the total IgE levels in children without atopic sensitization (hereafter defined as 'normal' t-IgE levels) and to test their usefulness in predicting atopic sensitization. Methods The German Multicentre Allergy Study ( MAS), a birth cohort with 1314 recruited newborns, began in 1990 and examined the participants until age 20 years. Total and specific IgE (t-IgE, s-IgE) were analyzed with a fluorescent enzyme immunoassay Immuno CAP ( TFS, Sweden) at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Participants were classified as 'never atopic' if all their available serum samples had negative response (cutoff: <0.35 kUA/L) for s-IgE to the nine common foodborne and airborne allergenic extracts (milk, egg, soy, wheat, house dust mite, cat, dog, birch, and grass) tested in the MAS birth cohort. By contrast, participants were defined as atopic if they had, for at least at one available serum sample, s-IgE≥0.35 kUA/L to at least one allergenic extract tested. The evolution of t-IgE levels in the 'never atopic' children was described by growth curves, estimated by exploiting a quantile regression model. A 'reference' percentile, based on the t-IgE value measured at age 5 years, was assigned to each child with no IgE sensitization at that age. Upward deviations from the own 'reference' quantile of t-IgE in atopic and 'never atopic' children were calculated and a ROC analysis was used to identify the best cutoff point for predicting atopic sensitization. Results Overall, 1113 of 1314 children were included in this analysis. Of these, 469 were 'never atopic' and 644 atopic. Quantile trajectories of t-IgE levels in 'never atopic' subjects were stable from 5 years of age, increased to a plateau at age 10-13 years, and decreased slightly afterward. The onset of atopic s-IgE responses was characterized by an upward deviation of serum t-IgE levels from their 'reference' trajectory. T-IgE quantiles predicted the onset of atopy with high efficiency ( AUC>80%). ROC analysis showed that deviations from the t-IgE level 'reference' quantile above 0.32, 0.41, 0.42, 0.30, and 0.58 kU/L (log-units) at 6, 7, 10, 13, and 20 years of age, respectively, predicted an atopic sensitization. Conclusion The growth curves of 'normal' serum t-IgE concentrations were estimated in 'never atopic' children; for each individual who was non-atopic at 5 years of age a 'reference' quantile was identified that represented the individual's 'normal' level of t-IgE production. Upward deviations of observed t-IgE levels from the own 'reference' quantile, from 6 to 20 years of age, predicted at each year the occurrence of atopic sensitization. Clinical Implications The trajectory of t-IgE levels can be elaborated since age 5 years in non-atopic children. A child whose t-IgE levels are consistently higher than those predicted by his/her growth curve may have developed atopic sensitization. [ABSTRACT FROM AUTHOR]

The so-called local allergic rhinitis ( LAR) has been proposed as a phenotype of rhinitis with Th2-driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of 'systemic' atopy (negative skin prick test and serum allergen-specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this 'Rostrum' was to critically discuss data and implications of the ' LAR concept' in paediatrics. In the natural history of rhinitis due to IgE-mediated reactions triggered by exposure to allergens, a ' LAR' can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to 'systemic' IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term 'local allergic rhinitis' may be inappropriate, as rhinitis is always 'local', while IgE sensitization can be either 'local' or 'systemic'. [ABSTRACT FROM AUTHOR]