RNA ‘tail length’ could help doctors tell bacterial and viral infections apart in critically ill children

Researchers from the Doherty Institute and The University of Melbourne have made a promising discovery that could help doctors quickly tell whether a very sick child has a bacterial or viral infection. This breakthrough could lead to faster treatment and help reduce the unnecessary use of antibiotics.

In a world-first study published in BMC Infectious Diseases, the team used a new technique called Nanopore direct RNA sequencing to study the tiny ‘tail’ on RNA, called poly(A) tail. This tail is a string of molecules added to the end of RNA, the messenger that carries instructions from our genes to the rest of the cell, that helps control how genes are used in the body. The length of the tail can change depending on what’s happening in the body, especially during infection.

When children are admitted in intensive care with sepsis, a life-threatening reaction to infection, figuring out whether the cause is bacterial or viral is critical. But there’s no quick and easy way to tell, and doctors often prescribe antibiotics as a precaution, before knowing the nature of the infection. However, antibiotics don’t help with viral infections, and overuse can lead to harmful side effects and antibiotic resistance.

The scientists used Nanopore direct RNA sequencing to analyse blood samples from children in intensive care who had sepsis, with confirmed bacterial or viral infections. By measuring poly(A) tails for thousands of genes, the researchers discovered an intriguing pattern: certain genes consistently had different tail lengths in viral infections compared to bacterial ones.

The University of Melbourne’s Dr Jingni He, Honorary Researcher at the Department of Clinical Pathology and Research Fellow at Monash University, who led the study, said the findings could improve diagnosis and treatment for critically ill children.

“We found that changes in RNA tail length could serve as biomarkers – signals that help us determine whether a patient has a bacterial or viral infection. This could lead to faster, more accurate diagnoses and guide more targeted treatment decisions,” said Dr He.

The University of Melbourne’s Professor Lachlan Coin, Laboratory Head at the Doherty Institute and senior author of the study, emphasised the significance of the discovery and its future potential.

“This is the first time scientists have identified that RNA tail lengths differ between bacterial and viral infections. Although the method is still in development, we hope it can eventually be used in hospital emergency departments and intensive care units to improve patient care, alongside standard tests,” said Professor Coin.

This research could lead to personalised, rapid diagnostic tests that ensure children get the right treatment faster. It also supports global efforts combatting drug-resistant bacteria by helping avoid the misuse of antibiotics.

Peer review: He J et al. Utilizing Nanopore direct RNA sequencing of blood from patients with sepsis for the discovery of co- and post-transcriptional disease biomarkers. BMC Infectious Diseases (2025). https://doi.org/10.1186/s12879-025-11078-z
   

Collaboration: This work is the result of a collaborative effort between the Doherty Institute, the University of Melbourne, the University of Queensland, University Children’s Hospital Zurich (Switzerland) and the RAPIDS study group.
 

Funding: This work was supported by the Australian Infectious Diseases Research Centre, Australian Research Council, Brisbane Diamantina Health Partners, Children’s Hospital Foundation, National Health and Medical Research Council (NHMRC), NOMIS foundation and the University of Queensland.