Immunothrombosis biomarkers for distinguishing COVID-19 patients from non-COVID septic pneumonia patients andfor predicting ICU mortality

ABSTRACT

Background: COVID-19 infection is characterized by immunothrombosis that likely reflects hypercoagulation, endothelial dysfunction, and increased formation of neutrophil extracellular traps. Aims: In this study, we investigated the utility of immunothrombosis biomarkers to distinguish between COVID-19 patients and non-COVID septic pneumonia patients. We also investigated the prognostic utility of the biomarkers in predicting ICU mortality in the two patients groups. Methods: The participants in this study were ICU COVID-19 patients ( n = 14), ICU non-COVID septic pneumonia patients ( n = 19), and age-and sex-matched healthy controls ( n = 14). Blood samples were collected on Days 4, 7, 10, and/or 14. We measured plasma levels of the following biomarkers thrombin-antithrombin (TAT) complexes, protein C, antithrombin, soluble TM, soluble EPCR, fibrinogen, D-dimer, cell-free DNA (cfDNA), and citrullinated histones (H3-Cit). Data analysis was based on binomial logit models and receiver operating characteristic curve analyses. Results: We identified 8 biomarkers that distinguish COVID-19 patients from healthy individuals cfDNA, D-dimer, sEPCR, PC, sTM, fibrinogen, H3-Cit, and TAT complexes. In comparison, 4 biomarkers distinguish COVID-19 from non-COVID septic pneumonia patients fibrinogen, sEPCR, antithrombin, and cfDNA. With respect to prognosis, the main predictors of ICU mortality differ between the two patient groups. In COVID-19 patients, non-survivors have higher sTM and H3-Cit compared with survivors. In septic pneumonia patients, non-survivor patients have lower levels of protein C and higher cfDNA levels compared with survivors. In addition, the most recent values of the biomarkers have stronger prognostic value compared to their Day 1 values. Conclusions: Our results suggest that fibrinogen, sEPCR, antithrombin, and cfDNA have utility for distinguishing COVID-19 patients from non-COVID septic pneumonia patients. Our data also suggest that the predictors of ICU mortality differ between the two patient groups sTM and H3-Cit for COVID-19 patients, and protein C and cfDNA for non-COVID septic pneumonia patients. These findings suggests that there are pathophysiological differences between the two patients groups.