Whole blood gene expression data of thrombotic and non-thrombotic critically ill COVID-19 patients

Background: COVID-19 has revealed novel pathological mechanisms, particularly hypercoagulability leading to increased thrombotic risk in critically ill patients. This study investigates transcriptional signatures associated with thrombosis development in COVID-19 intensive care unit (ICU) patients and evaluates their predictive potential. Methods: We performed whole blood transcriptional profiling of 57 mechanically ventilated COVID-19 patients, comparing those with thrombotic complications (TC, n=36) to those without (non-TC, n=21) using differential gene expression and machine learning approaches. Results: TC patients showed greater transcriptome disruption and 283 differentially expressed genes compared to non-TC patients. Key features included enhanced neutrophil activation, inflammatory responses, and monocyte activation alongside suppressed lymphocyte function. An OPLS-DA model achieved excellent classification performance (AUC=0.961, 95% CI: 0.905-0.997). The maltase-glucoamylase gene (MGAM) was the top discriminatory biomarker outperforming traditional clinical markers like D-dimer and C-reactive protein (AUC=0.94). Conclusions: Thrombotic complications in critically ill COVID-19 patients are characterized by distinct transcriptional signatures reflecting heightened neutrophil activation and inflammatory dysregulation. MGAM represents a novel potential biomarker that outperforms traditional clinical markers for identifying patients at high thrombotic risk, offering new opportunities for personalized risk stratification and management in severe COVID-19. This was a retrospective, observational study conducted at Erasmus medical center, The Netherlands, during the first wave of COVID-19 pandemic and precisely between 2nd March 2020 and 20th of April 2020. In brief, 77 patients with COVID-19 admitted to the ICU with ARDS were included in a biobank study (CIUM). If indicated by clinician, patients underwent computed tomographic pulmonary angiography, which was subsequently repeated 7 days after admission, or if the patient’s clinical condition abruptly deteriorated. Whole blood samples were available from 57 subjects at day 2 of ICU admission and were used in the presented research. Healthy controls were obtained from convalescent subjects enrolled as part of the MERMAIDS-ARI clinical observational study and were matched with cases based on age, gender, pulmonary, cardiovascular and metabolic disease infromation.