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\begin{document}

\title{Editorial Comment on ``Atopic outcomes at 2 years in the CORAL cohort,
born in COVID-19 lockdown''}



\author[1]{Sandoval Ruballos Mónica}%
\author[2]{CARMEN RIGGIONI}%
\author[3]{Jon Genuneit}%
\affil[1]{MSD Guatemala}%
\affil[2]{National University of Singapore Yong Loo Lin School of Medicine}%
\affil[3]{Universitat Leipzig Universitatsbibliothek Leipzig}%


\vspace{-1em}



  
  \date{June 18, 2024}


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Editorial Comment on ``\textbf{Atopic outcomes at 2 years in the CORAL
cohort, born in COVID-19 lockdown''}

Sandoval-Ruballos, M\selectlanguage{ngerman}ónica\textsuperscript{1}, Carmen
Riggioni\textsuperscript{2,3}, Jon Genuneit\textsuperscript{4}

\textsuperscript{1} Pediatric Allergy and Immunology Clinic, Guatemala,
Guatemala.

\textsuperscript{2}Department of Paediatrics, Yong Loo Lin School of
Medicine, National University of Singapore, Singapore.

\textsuperscript{3}Khoo Teck Puat-National University Children's Medical
Institute, National University Hospital, National University Health
System, Singapore.

\textsuperscript{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.\selectlanguage{english}
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Figure caption. Sadhbh Hurley\selectlanguage{english}
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REFERENCES:

\begin{enumerate}
\tightlist
\item
  Shin YH, Hwang J, Kwon R, et al. Global, regional, and national burden
  of allergic disorders and their risk factors in 204 countries and
  territories, from 1990 to 2019: A systematic analysis for the Global
  Burden of Disease Study 2019.~\emph{Allergy} . 2023;78(8):2232-2254.
  doi:10.1111/all.15807
\item
  Liu AH. Revisiting the hygiene hypothesis for allergy and
  asthma.~\emph{J Allergy Clin Immunol} . 2015;136(4):860-865.
  doi:10.1016/j.jaci.2015.08.012
\item
  Akdis CA. Does the epithelial barrier hypothesis explain the increase
  in allergy, autoimmunity and other chronic conditions? Nat Rev
  Immunol. 2021 Nov;21(11):739-751. doi: 10.1038/s41577-021-00538-7.
  Epub 2021 Apr 12. PMID: 33846604.
\item
  Hurley S, Franklin R, McCallion N, et al. Atopic outcomes at 2 years
  in the CORAL cohort, born in COVID-19 lockdown.~\emph{Pediatr Allergy
  Immunol} . 2023;34(9):e14013. doi:10.1111/pai.14013
\item
  O'Donovan SM, Murray DM, Hourihane JO, Kenny LC, Irvine AD, Kiely M.
  Cohort profile: The Cork BASELINE Birth Cohort Study: Babies after
  SCOPE: Evaluating the Longitudinal Impact on Neurological and
  Nutritional Endpoints. \emph{Int. J. Epidemiol.} 2015; 44 (3):
  764-775. 10.1093/ije/dyu157
\item
  Illi S, von Mutius E, Lau S, et al. The natural course of atopic
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  asthma.~\emph{J Allergy Clin Immunol} . 2004;113(5):925-931.
  doi:10.1016/j.jaci.2004.01.778
\item
  Hurley S, Franklin R, McCallion N, et al. Allergy-related outcomes at
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\item
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  doi:10.1111/pai.13273
\item
  Yucel E, Suleyman A, Hizli Demirkale Z, Guler N, Tamay ZU, Ozdemir C.
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  children with respiratory allergies?.~\emph{Pediatr Allergy Immunol} .
  2021;32(5):963-970. doi:10.1111/pai.13477
\item
  Munblit D, Greenhawt M, Brough HA, et al. Allergic diseases and
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  pediatrics.~\emph{Pediatr Allergy Immunol} . 2022;33(10):e13851.
  doi:10.1111/pai.13851
\end{enumerate}

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