A study in BMC Infectious Diseases identified gene activity patterns associated with severe COVID-19 in children, showing similarities with other serious respiratory infections. The research team examined blood samples from 333 children in South Africa, including those hospitalized with severe COVID-19, respiratory syncytial virus (RSV), and pulmonary tuberculosis (PTB), as well as healthy controls and mild COVID-19 cases. Their analysis revealed distinct differences in gene behavior between severe and non-severe infections.
More than 5,000 genes exhibited altered activity in children with severe infections, with 10 gene groups behaving similarly across all three conditions. This suggests shared immune and cellular responses. An additional 82 genes differentiated mild or asymptomatic COVID-19 from severe cases, potentially serving as predictive markers for disease progression.
Dr. Negusse Kitaba, a senior research fellow at the University of Southampton and lead researcher, said, “These findings provide new insights into the biological pathways involved in disease severity and highlight genes for further investigation as potential biomarkers and therapeutic targets.”
Heather Zar, a professor and director of the South African Medical Research Council Unit on Child & Adolescent Health at the University of Cape Town, emphasized that most research on childhood respiratory infections has focused on high-income settings. “There’s been limited research examining biological responses to these infections in African children. There have also been few studies on host gene expression in infants and children with COVID-19 globally, so this study helps to close an important evidence gap,” she said.
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John Holloway, a professor of allergy and respiratory genetics at the University of Southampton, said, “This study highlights the value of international collaboration in understanding childhood respiratory disease and provides a foundation for future research into why some children develop severe infection.”
The researchers observed that severe infections, whether from COVID-19, RSV, or PTB, triggered overlapping immune responses. This indicates common vulnerabilities in children’s immune systems rather than disease-specific mechanisms driving severity. The discovery suggests that broad immune pathways may play a larger role in determining outcomes than previously recognized.
The study was published in BMC Infectious Diseases, with the DOI 10.1186/s12879-026-14343-x. The research team cautioned that larger follow-up studies are necessary before these gene signatures can be applied in clinical practice.