Respiratory morbidity at age 4 across COVID-19 and pre-pandemic birth cohorts: the role of atopic risk.

Authors

Alma Kamar, Avigdor Mandelberg, NatalyRosenfeld, Diana Tasher, Marina Michleson, Adi Meridor Eisner, Adi Ovadia, Yaara Shen Cohen, Amit Manor, Keren Armoni Domany

Published in

European journal of pediatrics. Volume 185. Issue 11. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

The COVID-19 pandemic dramatically reduced early-life respiratory viral exposures, yet the long-term respiratory consequences for pandemic-born children remain unclear. We aimed to compare respiratory morbidity at age 4 between children born during versus before the pandemic and assess whether atopic risk modifies this association. This single-center birth cohort follow-up study included children born in February-March 2020 (COVID-19 cohort) and pre-pandemic controls born during the same period in 2019. Respiratory outcomes at age 4 were assessed using a structured telephone questionnaire (The International Study of Wheezing in Infants). The primary outcome was composite respiratory morbidity (CRM), defined as use of a short-acting bronchodilator (SABA), inhaled and/or oral corticosteroids, and/or emergency room visits for respiratory symptoms. Of 588 eligible children, 329 (55.9%) completed follow-up (139 COVID-19, 190 controls); baseline characteristics, including atopy prevalence, were comparable between cohorts. CRM during the fourth year of life was significantly more common in the COVID-19 cohort (39.6% vs. 27.4%, p = 0.02). In stratified analyses, CRM was markedly higher among atopic-risk pandemic-born children (atopic subgroup: n = 47 COVID-19, n = 68 controls) (66% vs. 27.9%, p < 0.001), but not among non-atopic children (26.1% vs. 27%). Multivariable logistic regression confirmed a significant COVID-19 cohort × atopy interaction for CRM (OR 5.04, 95% CI 1.83-13.89, p = 0.002), while neither factor alone was independently associated with the outcome.
 Birth during the COVID-19 pandemic was associated with increased preschool respiratory morbidity, particularly among children with atopic risk. These findings suggest that altered early-life microbial exposures may modify respiratory morbidity trajectories according to host atopic susceptibility.
• Children born during the COVID-19 pandemic had fewer respiratory infections and wheezing episodes in infancy due to reduced viral circulation. • Atopic predisposition is among the strongest risk factors for recurrent wheezing and persistent asthma in preschool children.
• Pandemic-born children show significantly higher composite respiratory morbidity at age 4, but exclusively among those with atopic risk (OR 5.04). • Neither pandemic birth nor atopy alone predicts excess morbidity-only their combination does, suggesting host susceptibility shapes long-term respiratory trajectories.

PMID:
42830320
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

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