Platelet activation in critically ill COVID-19 patients

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Microvascular, arterial and venous thrombotic events have been largely described during severe coronavirus disease 19 (COVID-19). However, mechanisms underlying hemostasis dysregulation remain unclear.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We explored two independent cross-sectional cohorts to identify soluble markers and gene-expression signatures that discriminated COVID-19 severity and outcomes.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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, <jats:italic>p</jats:italic> = 0.028 and AUC = 0.74, <jats:italic>p</jats:italic> = 0.0047, respectively). An optimal cutoff value 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. An unbiased gene set enrichment analysis revealed that critically ill patients had increased expression of genes related to platelet activation. Hierarchical clustering identified <jats:italic>ITG2AB</jats:italic>, <jats:italic>GP1BB</jats:italic>, <jats:italic>PPBP</jats:italic> and <jats:italic>SELPLG</jats:italic> to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of intubation was significant for <jats:italic>SELPLG</jats:italic> and <jats:italic>PPBP</jats:italic> (AUC = 0.8, <jats:italic>p</jats:italic> = 0.046 for both). An optimal cutoff value for <jats:italic>PBPP</jats:italic> was predictive of intubation with 100% NPV and 45% PPV, and for <jats:italic>SELPLG</jats:italic> with 100% NPV and 50% PPV.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We provide evidence that platelets contribute to COVID-19 severity. Plasma sP-selectin level was associated with severity and in-hospital mortality. Transcriptional analysis identified <jats:italic>PPBP/CXCL7</jats:italic> and <jats:italic>SELPLG</jats:italic> as biomarkers for intubation. These findings provide additional evidence for platelet activation in driving critical COVID-19. Specific studies evaluating the performance of these biomarkers are required.</jats:p> </jats:sec>