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Scientists Discover ‘Blood Fingerprint’ of Long COVID in Children, Paving Way for First Diagnostic Test

In a discovery that could transform how doctors diagnose and treat Long COVID in young patients, Italian researchers have identified a distinct molecular signature in children’s blood that proves the condition has clear biological markers. The groundbreaking study, published in Pediatric Research, reveals that Long COVID in children shares similar inflammatory patterns to those found in adults, effectively ending debate about whether the condition has a physical basis in young people.

Using advanced protein analysis and artificial intelligence, the research team examined blood samples from 112 children, comparing those with Long COVID to others who had acute COVID-19, inflammatory complications, or no infection history. The study found that children with Long COVID showed a unique pattern of inflammatory proteins in their blood, different from all other groups.

“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,” says Dr. Danilo Buonsenso, lead researcher at Università Cattolica del Sacro Cuore and pediatrician at Fondazione Policlinico Gemelli IRCCS.

The researchers developed an artificial intelligence model that could identify Long COVID cases with 93% accuracy, offering hope for the first objective diagnostic test for the condition. The model showed 86% specificity and 97% sensitivity in detecting cases based on blood protein patterns.

Most significantly, the study identified eight specific inflammatory proteins that were consistently elevated in children with Long COVID, including CXCL11, CXCL1, and CXCL8, which play crucial roles in inflammation and blood vessel formation. This protein signature mirrors patterns previously seen in adult Long COVID patients, suggesting similar underlying disease mechanisms across age groups.

“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,” explains Dr. Nicola Cotugno of the Bambino Gesù Children’s Hospital.

The study included rigorous controls, comparing 34 children with Long COVID against 32 with active infections, 27 with multisystem inflammatory syndrome (MIS-C), and 19 healthy controls. All children in the Long COVID group had symptoms persisting for at least eight weeks after initial infection, with impacts significant enough to disrupt daily activities.

Researchers found that children with persistent fatigue showed particularly high levels of FGF21, a protein involved in energy metabolism and muscle function. This finding aligns with recent adult studies linking Long COVID fatigue to mitochondrial dysfunction, suggesting potential treatment pathways.

The research represents a major step forward in understanding pediatric Long COVID, which affects approximately 0.5% of children exposed to SARS-CoV-2. While less common than in adults, the condition particularly impacts children over 10 years old, regardless of how severe their initial infection was.

These findings could lead to the development of routine blood tests for diagnosing Long COVID in children, potentially revolutionizing how the condition is identified and treated. The discovery of specific biological markers also opens new avenues for targeted therapies, offering hope to families struggling with this challenging condition.

Looking ahead, the research team has already begun collecting follow-up samples to track how these blood markers change as children recover, potentially providing insights into the condition’s duration and treatment effectiveness. The study authors emphasize the need for larger trials to validate these findings and develop standardized diagnostic tests.


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