Platelet activation in critically ill COVID-19 patients

Yatim, Nader; Boussier, Jeremy; Chocron, Richard; Hadjadj, Jérôme; Philippe, Aurélien; Gendron, Nicolas; Barnabei, Laura; Charbit, Bruno; Szwebel, Tali-Anne; Carlier, Nicolas; Pène, Frédéric; Azoulay, Célia; Khider, Lina; Mirault, Tristan; Diehl, Jean-Luc; Guerin, Coralie L.; Rieux-Laucat, Frédéric; Duffy, Darragh; Kernéis, Solen; Smadja, David M.; Terrier, Benjamin

BACKGROUND: Microvascular, arterial and venous thrombotic events have been largely described during severe coronavirus disease 19 (COVID-19). 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 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 ITG2AB, GP1BB, PPBP and SELPLG to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of intubation was significant for SELPLG and PPBP (AUC = 0.8, p = 0.046 for both). An optimal cutoff value for PBPP was predictive of intubation with 100% NPV and 45% PPV, and for SELPLG with 100% NPV and 50% PPV. CONCLUSION: 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 PPBP/CXCL7 and SELPLG 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13613-021-00899-1.