Eleonora Petito1, Emanuela Falcinelli1, Ugo Paliani2, Enrica Cesari1, Gaetano Vaudo3, Manuela Sebastiano1, Vittorio Cerotto4, Giuseppe Guglielmini1, Fabio Gori5, Marco Malvestiti1, Cecilia Becattini1, Francesco Paciullo1, Edoardo De Robertis6, Loredana Bury1, Teseo Lazzarini7, Paolo Gresele1. 1. Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy. 2. Division of Internal Medicine, ASL 1 Umbria, Città di Castello, Italy. 3. Unit of Internal Medicine, Terni University Hospital, Terni, Italy. 4. Section of Anesthesia, Intensive Care and Pain Medicine, Department of Emergency and Urgency, Città di Castello Hospital, Città di Castello, Italy. 5. Section of Anesthesia, Intensive Care, and Pain Medicine, Azienda Ospedaliera-Universitaria Santa Maria della Misericordia, Perugia, Italy. 6. Department of Surgical and Biomedical Sciences, Division of Anaesthesia, Analgesia, and Intensive Care, University of Perugia, Perugia, Italy. 7. Section of Anesthesia and Intensive Care, Presidio Alto Chiascio, USL Umbria 1, Gubbio, Italy.
Abstract
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. METHODS: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. METHODS: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.
Authors: Ellen McKenna; Richard Wubben; Johana M Isaza-Correa; Ashanty M Melo; Aisling Ui Mhaonaigh; Niall Conlon; James S O'Donnell; Clíona Ní Cheallaigh; Tim Hurley; Nigel J Stevenson; Mark A Little; Eleanor J Molloy Journal: Front Immunol Date: 2022-06-01 Impact factor: 8.786
Authors: Samantha M Morrissey; Anne E Geller; Xiaoling Hu; David Tieri; Chuanlin Ding; Christopher K Klaes; Elizabeth A Cooke; Matthew R Woeste; Zachary C Martin; Oscar Chen; Sarah E Bush; Huang-Ge Zhang; Rodrigo Cavallazzi; Sean P Clifford; James Chen; Smita Ghare; Shirish S Barve; Lu Cai; Maiying Kong; Eric C Rouchka; Kenneth R McLeish; Silvia M Uriarte; Corey T Watson; Jiapeng Huang; Jun Yan Journal: JCI Insight Date: 2021-05-10