Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls

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.

Impact:

  • Pediatric Long COVID has a distinct blood protein signature marked by increased ongoing general and endothelial inflammation.
  • This is the first study studying and documenting proinflammatory profile in blood samples of children with long COVID.
  • 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 proteomic profile was able to identify Long COVID with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97.
  • These findings may inform development of future diagnostic tests.

Source: Buonsenso, D., Cotugno, N., Amodio, D. et al. Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-03837-0  https://www.nature.com/articles/s41390-025-03837-0