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Immunothrombosis and plasma fibrinolytic function for pediatric COVID-19: a secondary analysis from the COVAC-TP

Anthony A Sochet1,2,3, Austin R Sellers2, Marisol Betensky4,2,3

  • 1Departments of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Blood Vessels, Thrombosis & Hemostasis
|August 6, 2025
PubMed

Insights

Inflammation contributes to blood clotting issues and reduced clot breakdown in children hospitalized with COVID-19 and MIS-C. These findings highlight inflammation

Area of Science:

  • Pediatric Hematology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • The interplay between fibrinolysis, inflammation, and prothrombotic risk in pediatric COVID-19 is not well understood.
  • Multisystem inflammatory syndrome in children (MIS-C) presents unique challenges in assessing thrombotic risk.

Purpose of the Study:

  • To investigate the association between plasma fibrinolytic capacity and proinflammatory cytokine concentrations in children hospitalized with COVID-19 and MIS-C.
  • To determine if cytokine concentrations differ by clinical phenotype and correlate with impaired fibrinolysis (hypofibrinolysis).

Main Methods:

  • Analysis of banked plasma specimens from children (<18 years) enrolled in the COVID-19 Anticoagulation in Children-Thromboprophylaxis trial.
  • Measurement of plasma coagulative and fibrinolytic function using clot formation and lysis (CloFAL) assay and modified mini-euglobulin clot lysis assay (ECLA).
  • Quantification of key proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) using Meso Scale Discovery assay and correlation analysis with fibrinolysis indices.

Main Results:

  • Increased coagulative function and impaired fibrinolytic function were observed, particularly in MIS-C patients.
  • Plasma cytokine concentrations showed significant correlations with markers of hypofibrinolysis (elevated modified mini-ECLA CLTR and reduced CloFAL FI).

Conclusions:

  • Inflammation plays a role in the hypercoagulability and hypofibrinolysis seen in hospitalized children with COVID-19-related illnesses.
  • These inflammatory-mediated hemostatic changes may contribute to the prothrombotic risk in this pediatric population.

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