Platelet activation in critically ill COVID-19 patients

Autor: Jérôme Hadjadj, David M. Smadja, Darragh Duffy, Celia Azoulay, Frédéric Rieux-Laucat, Tristan Mirault, Jean-Luc Diehl, Benjamin Terrier, Bruno Charbit, Nader Yatim, Laura Barnabei, Aurélien Philippe, Coralie L. Guerin, Nicolas Gendron, T.-A. Szwebel, Lina Khider, Frédéric Pène, Nicolas Carlier, Richard Chocron, Jeremy Boussier, Solen Kernéis
Přispěvatelé: Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Centre National de Référence Maladies Systémiques et Autoimmunes Rares, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. The study was also supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by a government grant managed by the Agence National de la Recherche as part of the 'Investment for the Future' program (ANR-10-IAHU-01), and by grants from the Agence National de la Recherche: ANR-flash Covid19 'AIROCovid' and 'CoVarImm'. We also acknowledge funding from the Institut Pasteur for Covid19 research. J.H. is a recipient of an Institut Imagine MD-PhD fellowship program supported by the Fondation Bettencourt Schueller. L.B. is supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) program of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the Future' program. We thank AP-HP for promotion of the SARCODO Project. We thank the unit of clinical research URC HEGP CIC-EC1418 (Natacha Nohile, Pauline Jouany and Dr Juliette Djadi-Prat) and Helene Cart-Grandjean from AP-HP for their involvement in SARCODO project. SARCODO project was supported by grants of ANR (Fondation de France) and Appel d'offre AP-HP mécénat crise COVID-19 from GHU APHP.CUP., We would like to acknowledge all nurses, technicians and physicians involved in all department involved in COVID-19 patients management in APHP.CUP hospitals, for their help in taking care of patients and including them in the study, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Vougny, Marie-Christine, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé - - AIROCovid192020 - ANR-20-COVI-0022 - COVID-19 - VALID, Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence - - CoVarImm2020 - ANR-20-COVI-0053 - COVID-19 - VALID, Génétique et Epigénétique Nouvelle Ecole - - GENE2017 - ANR-17-EURE-0013 - EURE - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Annals of Intensive Care
Annals of Intensive Care, SpringerOpen, 2021, 11 (1), pp.113. ⟨10.1186/s13613-021-00899-1⟩
Annals of Intensive Care, Vol 11, Iss 1, Pp 1-12 (2021)
Annals of Intensive Care, 2021, 11 (1), pp.113. ⟨10.1186/s13613-021-00899-1⟩
ISSN: 2110-5820
DOI: 10.1186/s13613-021-00899-1⟩
Popis: 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.
Databáze: OpenAIRE
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