Thrombosis pathways in COVID-19 vs. influenza-associated ARDS: a targeted proteomics approach

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 =.022 and −1.78, p =.022, respectively). However, total pathway analysis indicated increased activation of endothelium (z-score 0.2 [−0.3–1.03] vs. 0.98 [−2.5–−0.3], p =.027), platelets (1.0 [−1.3–3.0] vs. −3.3 [−4.1–−0.6], p =.023) and coagulation (0.8 [−0.5–2.0] vs. −1.0 [−1.6–1.0], p =.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.