Thrombosis pathways in COVID‐19 vs. influenza‐associated ARDS: A targeted proteomics approach
Journal of Thrombosis and Haemostasis, 2022
Rademaker E., Doorduijn D., Kusadasi N., Maas C., Drylewicz J., Huisman A., Hoefer I., Bonten M., Derde L., Rooijakkers S., Cremer O.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background: Pulmonary embolism (PE) occurs in one-third of critically-ill COVID-19 patients. Although prior studies identified several pathways contributing to thrombogenicity, it is unknown whether this is COVID-19-specific or also occurs in ARDS patients with another infection.
Objective: To compare pathway activity among patients having COVID-19 with PE (C19PE+), COVID-19 without PE (C19PE-), and influenza-associated ARDS (IAA) using a targeted proteomics approach.
Methods: We exploited an existing biorepository containing daily plasma samples to carefully match C19PE+ cases to C19PE- and IAA controls on mechanical ventilation duration, PEEP, FiO2, and cardiovascular-SOFA (n=15 per group). Biomarkers representing various thrombosis pathways were measured using proximity extension- and ELISA-assays. Summed z-scores of individual biomarkers were used to represent total pathway activity.
Results: We observed no relevant between-group differences among 22 biomarkers associated with activation of endothelium, platelets, complement, coagulation, fibrinolysis or inflammation, except sIL-1RT2 and sST2, which were lower in C19PE- than IAA (log2-Foldchange -0.67, p=0.022 and -1.78, p=0.022, respectively). However, total pathway analysis indicated increased activation of endothelium (z-score 0.2 [-0.3 – 1.03] versus 0.98 [-2.5 – -0.3], p=0.027), platelets (1.0 [-1.3-3.0] versus -3.3 [-4.1 – -0.6], p=0.023) and coagulation (0.8 [-0.5 – 2.0] versus -1.0 [-1.6 – 1.0], p=0.023) in COVID-19 patients (C19PE+/C19PE- groups combined) compared to IAA.
Conclusion: We observed only minor differences between matched C19PE+, C19PE-, and IAA patients, which suggests individual biomarkers mostly reflect disease severity. However, analysis of total pathway activity suggested upregulation of some distinct processes in COVID-19 could be etiologically related to increased PE-risk.