AI-based blood test could revolutionize diagnosis of Long Covid in children

One day Long Covid in children could be objectively diagnosed with a blood test, thanks to the help of Artificial Intelligence (AI). In fact, a study by the Università Cattolica del Sacro Cuore, Rome campus - Fondazione Policlinico Universitario Agostino Gemelli IRCCS and the Ospedale Pediatrico Bambino Gesù IRCCS, has highlighted the molecular signature of Long Covid in plasma in pediatric age and used an AI tool capable of making the diagnosis based on the results of the blood sample, with 93% accuracy.

The study was published in the journal 'Pediatric Research', by Nature Group, and was led by Dr. Danilo Buonsenso, researcher in general and specialist paediatrics at the Faculty of Medicine and Surgery of the Catholic University and paediatrician at the Pediatric Infectious Diseases Operative Unit of the Fondazione Policlinico Gemelli IRCCS, together with Dr. Nicola Cotugno, at the Complex Operative Unit of Clinical Immunology and Vaccinology of the Bambino Gesù IRCCS Paediatric Hospital.

The study involved, among others, Dr. Piero Valentini, researcher in General and Specialist Paediatrics at the Faculty of Medicine and Surgery of the Catholic University and director of the Paediatric Infectious Diseases Operative Unit of the Fondazione Policlinico Gemelli IRCCS, and Dr. Paolo Palma, head of the Complex Operative Unit of Clinical Immunology and Vaccinology of the Bambino Gesù Children's Hospital IRCCS.

Background

Long Covid affects on average 0.5% of pediatric patients exposed to SARS-CoV-2. This condition, also known as Post COVID or Post-Acute Sequelae of SARS-CoV-2, is characterized by the persistence of signs and symptoms for at least 8-12 weeks, symptoms not present before the viral infection, with a negative impact on daily life. Long COVID affects patients of almost all age groups, and among pediatric patients those older than 10 years seem to be most affected, regardless of the severity of the initial infection.

In adults, the Long COVID 'sign' was found in the blood of adults, but a similar finding in the paediatric population was lacking.

The study

The experts analyzed the blood of 112 young people aged 0-19 years, of whom 34 had a clinical diagnosis of Long COVID, 32 had the active infection at the time of the study, 27 had Multisystem Inflammatory Syndrome (MIS-C, a severe hyper-inflammatory reaction that almost always requires intensive care) and 19 healthy control peers.

The experts performed an analysis of the blood protein component (proteomics) and saw that, compared to the control groups, the pediatric Long COVID was characterized by a higher presence in plasma of the pro-inflammatory and pro-angiogenic chemokine sets CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a. An artificial intelligence model based on proteomic profiling was able to identify long Covid with an accuracy of 0.93, a specificity of 0.86 and a sensitivity of 0.97.

Conclusions

Long Covid in pediatric patients also presents a distinct protein signature in plasma, characterized by increased inflammation in general and at the level of blood vessel walls (endothelia), as already seen in adults. The discovery could lead to the development of a simple routine diagnostic test based on a blood sample, allowing timely and complete care of the pediatric patient with Long Covid.

The immunological data produced in this study provide the evidence needed to identify therapeutic targets to be tested in efficacy and safety studies in pediatric Long Covid."

Dr. Nicola Cotugno, Complex Operative Unit of Clinical Immunology and Vaccinology of the Bambino Gesù IRCCS Paediatric Hospital

'This work demonstrates incontrovertibly that Long Covid, also in pediatric age, is an organic immune-mediated disease, for which new funding is needed to study the best therapeutic approaches,' Dr Buonsenso concludes.

Source:
Journal reference:

Buonsenso, D., et al. (2025). Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls. Pediatric Research. doi.org/10.1038/s41390-025-03837-0.

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