Editorial Comment on “Atopic outcomes at 2 years in the CORAL cohort, born in COVID-19 lockdown”Sandoval-Ruballos, Mónica1, Carmen Riggioni2,3, Jon Genuneit41 Pediatric Allergy and Immunology Clinic, Guatemala, Guatemala.2Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.3Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, National University Health System, Singapore.4 Pediatric Epidemiology, Department of Pediatrics, Medical Faculty, Leipzig University, Leipzig, GermanyAtopic conditions have been on the rise globally, particularly in industrialized nations.(1) This phenomenon has spurred interest in the potential connection between the surge in allergic disorders and modern lifestyles characterized by reduced microbial exposure and increased hygiene practices. While the hygiene theory proposes that the early childhood microbial environment plays a pivotal role in shaping immune system development, reducing the risk of atopic conditions, more recent findings have emphasized the role of a defective epithelial barrier. This recent perspective suggests that the upsurge in agents damaging the epithelial barrier, associated with industrialization and modern living, is at the core of the escalation of allergic, autoimmune, and other chronic conditions. Notably, these effects may have intensified during the pandemic. (2) (3)The SARS-CoV-2 pandemic in early 2020 prompted various lockdowns and stringent hygiene measures, offering an intriguing opportunity to investigate the impact of these altered environmental factors on the prevalence of atopic conditions. The CORAL study is a longitudinal observational project, following 365 infants born in Ireland, during the initial pandemic period (March-May 2020) from enrollment to 24 months of age. (4) The authors compared the occurrence of allergic diseases with a pre-pandemic Irish cohort (BASELINE study 2008-2011). (5) This investigation aims to shed light on the pandemic’s potential impact on infant allergic disease development.At first glance, the CORAL cohort exhibited higher rates of atopic dermatitis (AD) at both 12 and 24 months compared to BASELINE. However, this finding may reflect a gradual increase in AD incidence within their population, given that the BASELINE cohort was born about one decade earlier. Alternatively, the early-life environment during the lockdowns may have played a role. In addition, the authors delineated three patterns of AD. A more severe AD phenotype was noted among infants with persistent AD diagnosis at 24 months, and AD-persistent infants were more likely to be sensitized. This observation aligns with prior studies, highlighting the significance of severity, and atopic sensitization as relevant determinants of AD prognosis.(6)While AD rates were higher in the CORAL cohort, they exhibited lower rates of food sensitization and allergy compared to BASELINE, particularly significant in peanut sensitization and egg allergy, with a non-significant trend towards lower peanut allergy. Importantly, parents received complementary feeding advice at 6 months, emphasizing early peanut introduction. Therefore, these outcomes may be attributed to recommended early allergen introduction, along with other factors like increased breastfeeding, fewer infections during the first 12 months (7), lower antibiotic exposure, and sustained dietary allergen exposure during lockdown. The relevance of early allergen introduction, especially for peanut and egg, has gained prominence in international guidelines more recently, owing to accumulating evidence underscoring its role in directly reducing the development of food allergy (8).At 24 months, antibiotic usage and childcare outside home increased AD likelihood potentially linked to decreased infection rates and antibiotic use in children not attending daycare, preserving microbiota integrity. Intriguingly, despite more AD cases in children attending daycare, they exhibited lower allergic sensitization rates. Aeroallergen sensitization at 24 months was more pronounced among children cared for solely at home, thus reflecting environmental influence. From a theoretical perspective, it is plausible that the lockdown measures, which led to a substantial increase in indoor confinement, may have resulted in heightened exposure to indoor allergens,(9) consequently leading to higher sensitization rates. Furthermore, allergic sensitization at 12 and 24 months was associated with AD at both time points and with asthma diagnosis at 24 months.Despite its valuable insights, the CORAL study has limitations, including a small cohort size and potential selection bias, as it represented only 12% of eligible children. Here, high breastfeeding rates and low parental smoking rates may limit generalizability. Additionally, the small sample size might hinder the identification of associations that might be evident in larger cohorts.Other studies conducted during the pandemic have primarily focused on assessing the impact on allergic conditions during lockdowns. They have often reported positive effects of interventions such as hygiene, mask usage, and social distancing in reducing air pollution and lowering infection rates, potentially resulting in a reduced impact on allergic conditions (10). The CORAL study stands out among these studies due to its specific objective of evaluating the effect of lockdowns on the incidence of allergic diseases. Finally, it provides valuable insights into how the pandemic have influenced the health of infants born during this period. While the increased incidence of AD initially raises concerns, the lower rates of food sensitization and allergies suggest the positive effects of evolving allergy practices, particularly early allergen introduction. Furthermore, the beneficial impacts of lockdown, such as increased breastfeeding and reduced antibiotic use, may outweigh the anticipated risks associated with reduced early-life microbial exposures.This study enhances our understanding of the real-world impact of early-life environments on allergic disease risk. Continuous monitoring of the CORAL cohort into later childhood will reveal the lasting consequences of being born during the pandemic. These findings underscore the intricate interplay between environmental factors, infant health, and the development of allergies in a rapidly evolving landscape of healthcare practices.

Background: The prevalence of food allergies (FA) in children increased rapidly at the turn of the century. The EuroPrevall study identified Germany as a country with very high prevalence of FA at that time. Using two large German birth cohorts we provide an update of the status quo ten years later. Methods: KUNO Kids and Ulm SPATZ Health studies are two ongoing prospective birth cohorts. Information on FA was obtained by questionnaires at birth and after 6, 12 and 24 months. Univariate logistic regression analyses were performed to investigate risk factors during pregnancy, birth and early childhood. Results: In 1139 and 1006 children from KUNO Kids and SPATZ the point prevalence of parent-reported FA symptoms at the ages of 1 and 2 years was 13.2% and 13.9 % in KUNO Kids. Doctor’s diagnosed FA at 1 and 2 years was 2.4% and 2.7% in KUNO Kids and 2.3% and 3% in SPATZ. Cow’s milk and citrus fruits were most frequently suspected by parents to cause FA symptoms. Atopy in the child was associated with a higher frequency of FA at any time, whereas atopy in first degree relatives was only associated with FA at year 1. Smoke exposure during pregnancy was a risk for FA at age 2. Conclusion: The prevalence of food allergy seems to have plateaued in the last 10 years in Germany. FA is often suspected by parents but only rarely diagnosed by oral food challenge. Risk factor analysis may help to establish personalized health approaches.

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30th September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE-mediated food allergy. Methods: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1st October 2012 to 30th June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS-2 tool. All evaluation will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta-analysis will be performed if there are three or more studies of the same index test and food. Results: A protocol for the systematic review and meta-analyses is presented and was registered using Prospero prior to commencing the literature search. Discussion: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.

Research data derived from observational studies are accumulating quickly in the field of allergy and immunology and a large amount of observational studies are published every year. The aim of the present study was to evaluate the adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist by papers published in the three European Academy of Allergy and Clinical Immunology journals, during the period 2009-2018. To this end, we conducted a bibliographic study of up to eight randomly selected papers per year per Journal. Our literature search resulted in 223 papers. Among those, 80, 80 and 63 records were from Pediatric Allergy and Immunology, Allergy and Clinical and Translational Allergy, respectively; the latter was published only from 2011 on. Prospective, case-control, and cross-sectional designs were described in 88, 43, and 92 papers, respectively. Full reporting of all STROBE items was present in 47.4%, 45.6%, and 41.2% for the cohort, cross-sectional, and case-control studies, respectively. Generally, no time trend in adherence of reporting STROBE items was observed, apart from reporting funding, which increased from 60% in 2009/2010 to more than 90% in 2018. We identified a cluster of STROBE items with low proportions of full reporting constituted by the items on reporting study design in the title and methods, variables types along with their measurement/assessment, bias and confounding, study size, and grouping of variables. It appears that the STROBE checklist is a suitable tool in observational allergy epidemiology. However, adherence to the STROBE checklist appeared suboptimal.

Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic “real-world” database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. There is a need to establish more AIT registries that collect data in a cohesive way, using standardised protocols. This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.