Editorial Comment on “Atopic outcomes at 2 years in the CORAL cohort, born in COVID-19 lockdown”

Sandoval-Ruballos, Mónica¹, Carmen Riggioni^2,3, Jon Genuneit⁴

¹ 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, Germany

Atopic 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.