Dysregulated primary hemostasis in critically ill COVID-19 patients (preprint)

ABSTRACT

Background: Microvascular thrombosis, as well as arterial and venous thrombotic events, have been largely described during severe Coronavirus disease 19 (COVID-19). Therapeutic anticoagulation has been proposed in critical patients, however mechanisms underlying hemostasis dysregulation remain unclear. Methods: We explored two independent cross-sectional cohorts to identify soluble markers and gene-expression signatures that discriminated COVID-19 severity and outcomes. Results: We found that elevated soluble (s) P-selectin at admission was associated with disease severity. Elevated sP-selectin was predictive of intubation and death (ROC AUC = 0.67, p = 0.028 and AUC = 0.74, p = 0.0047, respectively). An optimal cutoff value of 150 NC (normalized concentration) was predictive of intubation with 66% negative predictive value (NPV) and 61% positive predictive value (PPV), and of death with 90% NPV and 55% PPV. Next, an unbiased gene set enrichment analysis revealed that critically ill patients had increased expression of genes related to primary hemostasis. Hierarchical clustering identified ITG2AB, GP1BB, PPBP and SELPLG to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of mechanical ventilation was significant for SELPLG and PPBP (AUC = 0.8, p = 0.046 for both markers). An optimal cutoff value for PBPP was predictive of mechanical ventilation with 100% NPV and 45% PPV, and for SELPLG was predictive of mechanical ventilation with 100% NPV and 50% PPV.Conclusion: We provide evidence that platelets contribute to disease severity with the identification of sP-selectin as a biomarker for poor outcome. Transcriptional analysis identified PPBP and SELPLG RNA count as biomarkers for mechanical ventilation. These findings provide rationale for novel therapeutic approaches with antiplatelet agents.