(521) Inflammation and Hypofibrinolysis in Pediatric COVID-19: A Secondary Analysis of the COVAC-TP Trial

Monday, February 24, 2025

2:30pm – 3:30pm Eastern Time

Location: Connections Central - RST 09

First Author(s)

Austin R. Sellers, DO, MS

St Petersburg, Florida, USA

Co-Author(s)

MB

Marisol A. Betensky, MD

Assistant Professor, Pediatrics
Johns Hopkins
St Petersburg, Florida, United States
JM

John M. Morrison, MD, PhD

Assistant Professor, Pediatrics
Johns Hopkins University, Johns Hopkins All Children's Hospital, United States
DA

Dina Ashour, MS

Biostatistician
Johns Hopkins All Children's Hospital, United States
JF

Jamie Fierstein, PhD

Biostatistician / Epidemiologist
Johns Hopkins All Children's Hospital, United States
SB

Steven Bruzek, MS

Florida, USA
VI

Vera Ignjatovic, PhD

Professor, Pediatrics
Johns Hopkins All Children's Hospital, United States
NG

Neil A. Goldenberg, MD, PhD

Professor, Pediatrics and Internal Medicine
Johns Hopkins All Children's Hospital, United States
Anthony A. Sochet, MD,

Johns Hopkins All Childrens Hospital
St Petersburg, Florida, USA

Introduction: We sought to investigate the potential association between measures of plasma coagulative and fibrinolytic capacity with concentrations of thrombo-inflammatory cytokines among children hospitalized for SARS-CoV-2-related illnesses, including primary COVID-19 infection and multisystem inflammatory syndrome in children (MIS-C).

Methods: Banked plasma specimens serially collected during the hospital course of children aged < 18 years admitted for primary COVID-19 or MIS-C and enrolled in the COVID-19 Anticoagulation in Children – Thromboprophylaxis multicenter trial (COVAC-TP, www.clinicaltrials.gov, NCT04354155), an open-label, multicenter, phase 2 clinical trial between July 2020 - May 2021. Plasma coagulative and fibrinolytic function were measured via the Clot Formation and Lysis (CloFAL) assay and the modified mini-euglobulin clot lysis assay (modified mini-ECLA). Plasma concentrations of thromboinflammatory cytokines (i.e., interleukins [IL] -1β, -6, and -8 and tumor necrosis factor [TNF]-α) were measured via a MesoScale Discovery assay, with correlations evaluated using Spearman testing.

Results: Among 38 participants enrolled in the COVAC-TP trial (18 with COVID-19 and 20 with MIS-C), 132 banked plasma specimens were analyzed. Increased coagulative function (i.e., elevated CloFAL area under the curve) and impaired fibrinolytic function (i.e., reduced CloFAL fibrinolytic index and elevated modified-mini ECLA clot lysis time ratio [CLTR]) were observed for all participants. This was most notably among those with MIS-C as compared to primary COVID-19 infection. Plasma thromboinflammatory cytokine levels including IL-6, -8, and TNF-α were elevated in all subjects and correlated with elevated modified mini-ECLA CLTR representing impaired fibrinolysis).

Conclusions: Findings from this secondary analysis of banked specimens from the COVAC-TP Trial suggest both hypercoagulability and hypofibrinolysis may be mediated in part by proinflammatory cytokines and contribute to the prothrombotic state in children hospitalized for COVID-19 related illness.