ABSTRACT
Background: Galectin-3 is a beta-galactoside-binding lectin that has been described to be overexpressed in inflammation, atherosclerosis, and in myocardial fibrosis. In COVID-19, galectin-3 has been proposed as an important regulator of the inflammatory response and fibrosis processes. The role of galectin-3 as a platelet activator and thrombosis enhancer has been also recently described. However, the role of galectin-3 in the thrombotic risk in COVID-19 hasn't been studied extensively. Method(s): Patients with moderate to severe COVID-19 were included in the study. Hospitalized patients with acute respiratory diseases without COVID-19 were examined as controls. We compared the levels of galectin- 3, soluble ST2, tissue factor and tissue factor activity (TFa) as well as several other markers of increased thrombogenicity in both groups. The correlations between galectin-3 and coagulation as well as inflammation markers were assessed. The SOFA score was used as a marker for the clinical outcome. Result(s): 93 patients were included into the study of which 56 were SARS-CoV-2 positive (COV+) and 37 were SARS-CoV-2 negative controls (COV-). Galectin-3 levels were higher in the COV+ group (median 7.10 ng/ml [IQR 4.61-9.81] vs. 5.47 ng/ml [3.63-6.66] p=0.016) as well as the TFa (median 334.48 pM [115.19-632.58] vs. 134.02 pM [86.92- 206.66]) and the ST2 levels (median 5.49 ng/ml [2.40-9.28] vs. 2.19 ng/ml [0.66-3.91] p<0.001). We also observed a positive correlation between galectin-3 and IL-6 (r=0.559, p<0.001), ST2 (r=0.332, p=0.005), SOFA score (r=0.441, p=0.003), von Willebrand factor (r=0.401, p<0.001), plasminogen (r=0.361, p=0.001), antithrombin (r=0.453, p<0.001), and Ddimer (r=0.377, p=0.001). Conclusion(s): In patients with acute respiratory diseases, especially with COVID-19, galectin-3 is a marker for increased hypercoagulability and worse clinical outcome. Galactin-3 might be a useful therapeutic target for patients with COVID-19.
ABSTRACT
Background: Hemostasis is dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). However, patients with respiratory diseases other than COVID-19 can also show disturbed coagulation reactions during the acute inflammatory process. Parameters of coagulation and platelet function are here compared between patients with upper respiratory infections with and without COVID-19 and are related to the clinical outcome. Methods: Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COVpos) and SARS-CoV2-negative (COVneg) status were included. We assessed several parameters of coagulation and fibrinolysis as well as adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array. The SOFA score was assessed as marker of the clinical outcome. Results: 87 patients were included in the study of which 50 were COVpos and 37 were COVneg. Von Willebrand factor was significantly higher in COVID positive patients compared to the control group (4456,4 mU/ml [2701,4;9067,0] vs. 2528,0 mU/ml [1301,2;3693,8], p<0,001). COVID-positive patients exhibited also more tissue plasminogen activator in the circulating blood than COVID-negative patients with an respiratory infection (11,4 mU/ml [7,2;24,6] vs. 7,3 mU/ml [4,9;10,5], p=0,001). ADP, TRAP-, and AA-induced platelet reactivity was significantly higher in COVpos than in COVneg patients. The SOFA score was higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. The SOFA score correlated significantly with parameters of coagulation and platelet function. A larger percentage of classical and intermediate monocytes, and of CD4pos T cells (TH) aggregated with platelets in COVpos than in COVneg patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. IL-1RA and IL-6 levels correlated with the SOFA score in COVpos but not in COVneg patients, indicating a COVID-19-specific mechanism. Conclusion: In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with parameters of coagulation and platelet function. Dysregulated coagulation and platelet hyperreactivity were associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity. Funding Acknowledgement: Type of funding sources: None.