Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls
Pediatric Research, 2025
Buonsenso D., Cotugno N., Amodio D., Pascucci G., Di Sante G., Pighi C., Morrocchi E., Pucci A., Olivieri G., Colantoni N., Romani L., Rotili A., Neri A., Morello R., Sali M., Tremoulet A., Raffaelli F., Zampino G., Rossi P., Valentini P., Palma P.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases Pediatrics | Patient Stratification | Plasma | O Olink Target 96 |
Abstract
Background
Recent proteomic studies have documented that Long COVID in adults is characterized by a pro-inflammatory signature with thromboinflammation. However, if similar events happen also in children with Long COVID has never been investigated.
Methods
We performed an extensive protein analysis of blood plasma from pediatric patients younger than 19 years of age Long COVID and a control group of children with acute COVID-19, MIS-C, and healthy controls resulted similar for sex distribution and age. Children were classified as Long COVID if symptoms persisted for at least 8 weeks since the initial infection, negatively impacted daily life and could not be explained otherwise.
Results
112 children were included in the study, including 34 children fulfilling clinical criteria of Long COVID, 32 acute SARS-CoV-2 infection, 27 MIS-C and 19 healthy controls. Compared with controls, pediatric Long COVID was characterized by higher expression of the proinflammatory and pro-angiogenetic set of chemokines CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a. A Machine Learning model based on proteomic profile was able to identify LC with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97.
Conclusions
Pediatric Long COVID patients have a well distinct blood protein signature marked by increased ongoing general and endothelial inflammation, similarly as happens in adults.