Allergic diseases such as eczema, asthma, and food allergies have become increasingly common among children worldwide, particularly in high-income countries. These conditions can significantly affect a child’s quality of life and place a long-term burden on families and healthcare systems. While genetic susceptibility plays a role, growing evidence points to environmental changes, especially during the early stages of life, as key drivers of this trend.

Hygiene hypothesis

One influential explanation is the hygiene hypothesis, which proposes that reduced microbial exposure in early childhood, due to modern sanitation, urban lifestyles, and smaller family sizes, may disrupt the natural training of the immune system, increasing susceptibility to allergies. This theory has evolved to highlight the importance of the human microbiome, the diverse community of microorganisms living in and on our bodies, as a crucial factor in immune development. Early-life exposure to a rich and varied microbiome is now believed to help build immune tolerance and reduce allergy risk.

The CORAL study builds on these ideas, investigating how microbial and environmental exposures in infancy, particularly during the unique circumstances of the COVID-19 pandemic, may influence the development of allergic diseases in children.

​The CORAL (Impact of Corona Virus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) study is a longitudinal research project that investigates the effects of the COVID-19 pandemic’s social distancing measures on infant health, particularly focusing on the gut microbiome and developmental outcomes. This was an observational study with no control group available, historical Irish and international data was used for a comparison. This study offers valuable insights into how reduced microbial exposure and limited social interactions during critical periods of infant development can influence health trajectories.​

The CORAL study enrolled 365 infants born during the country’s first lockdown period. Ireland had one of the longest and strictest lockdowns. Participants attended research appointments at 6, 12, and 24 months of age, during which comprehensive assessments were conducted.

Gut microbiome

One of the primary objectives of the CORAL study was to examine how pandemic-related restrictions affected the gut microbiota of infants born during the early stages of the pandemic. The findings revealed significant differences in the microbiome composition of these infants compared to those born before the pandemic. Specifically, infants in the CORAL cohort exhibited:​

• Increased levels of bifidobacteria: There was a higher relative abundance of bifidobacteria in the gut microbiota of CORAL infants. This is often associated with beneficial health outcomes, including immune system development and protection against pathogens; and ​
• Decreased levels of clostridia: Conversely, levels of Clostridia, bacteria typically acquired from environmental exposure, were significantly lower. This reduction was linked to decreased microbial exposure due to limited interactions outside the household during lockdown periods. ​

These microbiota differences were not merely academic; they had real-world implications for allergy development. The study found that:​

• Lower incidence of allergic conditions: Despite the altered microbiome, the prevalence of allergic diseases such as atopic dermatitis and food allergies did not increase in the CORAL cohort. In some cases, there was even a reduction in allergic sensitisation compared to pre-pandemic levels. ​

This outcome suggests that while reduced microbial exposure during infancy can lead to changes in microbiota composition, other factors, such as increased breastfeeding and reduced antibiotic use during the pandemic, may have mitigated potential negative impacts on allergy development. ​

Developmental and behavioural outcomes

Beyond the microbiome, the CORAL study also assessed the developmental and behavioural outcomes of infants born during the pandemic. Several key observations were made:​

• Communication skills: Infants in the CORAL cohort scored lower on communication milestones compared to a pre-pandemic cohort. For instance, significantly fewer CORAL infants could say a definite word, point, or wave bye-bye at 12 months. These differences persisted at 24 months, with communication scores remaining significantly lower in the CORAL group. This study demonstrates that small social circles have led to feelings of isolation and loneliness among parents during the pandemic. In addition to small social circles, one in four of the infants in the cohort had never met another similarly aged child by the age of 12 months. Only time will tell how limited social interaction and lack of peer contact will affect the development of social communication skills in these babies;
• Gross motor skills: There were slight differences in gross motor development, with CORAL infants showing marginally lower scores. However, these positive differences were less pronounced than the deficits observed in communication skills; and ​
• Personal-social skills: Fewer CORAL infants fell below the standard deviation cut-off for personal-social development, suggesting some resilience in this domain despite reduced social interactions. ​

These findings highlight that while certain developmental milestones, particularly in communication, were delayed, the overall impact on developmental and behavioural outcomes was relatively modest. It underscores the adaptability of infants but also points to the potential long-term effects of limited social interactions during critical periods of development.​

How the pandemic influenced outcomes

Several factors unique to the pandemic environment may have influenced these outcomes:​

• Increased breastfeeding: With families spending more time at home, there was a noted increase in breastfeeding rates. Breast milk is rich in nutrients and probiotics that support healthy microbiota development, potentially offsetting some negative impacts of reduced environmental microbial exposure; ​
• Reduced exposure to infections and antibiotics: The lockdown led to fewer infections among infants, resulting in lower antibiotic usage. This reduction likely preserved beneficial gut bacteria that might otherwise have been depleted by antibiotic treatments; and
• Altered social interactions: Limited interactions outside the home reduced infants’ exposure to diverse microbial environments. While this might have led to a less diverse microbiome, the aforementioned factors may have helped maintain a balance, preventing an increase in allergic conditions.​

Follow-on to CORAL study

Building upon the insights gained from the CORAL study, researchers have initiated the FLORAL (Follow-on to CORAL) study to further investigate the long-term health outcomes of children born during the pandemic. The primary objectives of the FLORAL study include:​

• Long-term follow-up: Re-examining the original CORAL cohort at five years of age to assess the persistence of observed health outcomes, particularly in relation to allergic conditions and immune system development; ​
• Comparative analysis: Recruiting a new cohort of 1,000 infants born in March to May 2025 to compare with the ‘lockdown babies’ born in 2020. This comparison aims to elucidate the enduring effects of pandemic-related environmental changes on child health and development; and ​
• Microbiome and allergy evaluation: To analyse gut microbiome patterns and their association with immune development and allergy risk in both cohorts.

The FLORAL study holds significant importance for several reasons:​

• Understanding long-term effects: It seeks to determine whether the benefits observed in the CORAL cohort, such as improved gut microbiome development and lower rates of certain allergic conditions, persist as children reach school age;
• Informing public health strategies: Insights from the study could inform public health recommendations regarding infant care practices, especially during times of societal disruptions like pandemics.; and
• Enhancing pandemic preparedness: By understanding how early-life isolation and altered microbial exposure influence lifelong health, the study aims to contribute to global efforts in pandemic readiness and inform strategies to mitigate adverse health outcomes during future public health crises.​ Member States of the World Health Organization have agreed to a global process to draft and negotiate a convention agreement or other international instrument under the Constitution of the World Health Organization to strengthen pandemic prevention, preparedness and response.

Conclusion

The CORAL study offers a comprehensive insight into how pandemic-induced social distancing measures reshaped the early-life microbial environment and developmental trajectory of infants. While reduced social interaction during lockdowns negatively impacted certain aspects of infant development, particularly communication skills, other changes, such as decreased antibiotic use and increased rates of breastfeeding, may have helped buffer some of these effects. Notably, the study also found that allergy rates among participating infants were lower than expected, suggesting that certain pandemic-related lifestyle shifts may have had protective effects on immune development. These findings offer valuable insights for future public health planning, highlighting the need to balance infection control measures with the preservation of developmental and health-promoting exposures during critical periods of infant development.

The forthcoming FLORAL study will build upon these findings, offering a deeper understanding of the long-term effects of these unique early-life experiences on child development and health. These studies collectively enhance our comprehension of how significant societal events can shape health outcomes across the lifespan.

Funding for the study came from Research Ireland, Temple St Foundation and Clemens von Pirquet Foundation.