Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 11, 2025 2 hours, 18 minutes ago
Medical News: Understanding how COVID-19 affects young immune systems
A major international study led by researchers from the University of Cape Town, the University of Southampton, the University College London, Imperial College London, and the University of Western Australia has revealed critical differences in how children’s immune systems respond to SARS-CoV-2 compared to other respiratory infections. The team examined blood samples from 333 children to uncover why some develop severe COVID-19 while others experience only mild or no symptoms.
New Study Reveals How COVID-19 Triggers Unique Immune Disruption in Children
The research compared children with mild or asymptomatic SARS-CoV-2 infection, those hospitalized with severe COVID-19, respiratory syncytial virus lower respiratory tract infection (RSV-LRTI), and pulmonary tuberculosis (PTB) against healthy controls. This
Medical News report found that the scientists used advanced RNA sequencing and gene expression profiling to map over 5,000 genes and identify immune patterns linked to disease severity.
Thousands of genes linked to disease severity
In severe pediatric COVID-19 cases, researchers discovered major changes in immune-related genes such as IFI27, OLFM4, CBX7, and IGF2BP3. These genes were associated with overactive inflammatory pathways and impaired lymphocyte regulation. The team observed strong activation of neutrophil degranulation and interferon gamma signaling—both hallmarks of heightened inflammation. Interestingly, while severe cases showed immune hyperactivity, they also exhibited depletion in critical immune cells, suggesting an imbalance that may worsen disease outcomes.
Children infected with RSV displayed distinct genetic signatures involving IFI44L, USP18, and SIGLEC1, highlighting interferon-driven antiviral responses. In contrast, those with pulmonary tuberculosis showed gene activation related to bacterial defense, particularly in pathways involving MMP8, LTF, and DEFA4.
Unraveling the cellular imbalance in severe COVID-19
The researchers found that severe COVID-19 in children led to depletion of up to 22 immune cell types, including macrophages, T cells, and CD8+ memory cells. Meanwhile, mild or asymptomatic infections maintained more balanced immune cell distributions. The study’s computational analysis identified ten key “gene modules” shared across all major respiratory infections but also revealed certain modules unique to severe COVID-19.
One specific gene cluster, known as Module 10, was linked to TRIM28 and TNFR2—genes tied to immune dysregulation and viral persistence. Other modules involved T-cell activation, olfactory signaling, and adaptive immunity, reflecting the complex interplay between inflammation and viral control in children’s lungs and bloodstream.
Potential biomarkers for predicting severity
To identify which genes might help forecast severe outcomes, the researchers used machine learn
ing. Ninety-three genes were recognized as strong predictors of severe COVID-19, including CBX7, TRAF1, NR3C2, RORC, and MID2. Some of these genes overlapped with those that distinguished RSV and TB, pointing to shared pathways in immune exhaustion and inflammation. Importantly, the study found that several of these genes could serve as potential therapeutic targets, as they already align with existing drug databases.
Why these findings matter
This groundbreaking research provides one of the most detailed maps of children’s immune responses to SARS-CoV-2 and other lung infections. It explains why some children remain symptom-free while others experience severe respiratory distress. The discovery of thousands of differentially expressed genes and depleted immune cells opens new doors for targeted therapies and early diagnostic tools. These insights may help in designing better vaccines and treatments specifically for pediatric populations in low- and middle-income countries.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2025.11.07.687132v1
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