Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19

• Published in: Thrombosis research Vol. 209; pp. 106 - 114
• Main Authors: Willems, L.H., Nagy, M., ten Cate, H., Spronk, H.M.H., Groh, L.A., Leentjens, J., Janssen, N.A.F., Netea, M.G., Thijssen, D.H.J., Hannink, G., van Petersen, A.S., Warlé, M.C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.01.2022; The Authors. Published by Elsevier Ltd
• Subjects: Blood coagulation; Cohort Studies; COVID-19; Endothelial cells; Endothelin-1; Hematology, Oncology, and Palliative Medicine; Humans; Inflammation; Pandemics; SARS-CoV-2; Blood coagulation; IL; CI; F; TAT; PKa; Inflammation; PSM; SMD; Endothelial cells; COVID-19; VWF:Ag; SD; RD; SARS-CoV-2; ET-1; CAR; NLRP3; α1AT; C1inh; PCR; ELISA; WHO; Interleukin; Standard Deviation; Standardized Mean Differences; C1 esterase inhibitor; Coronavirus Disease 2019; Factor; Polymerase Chain Reaction; World Health Organization; Enzyme-Linked Immunosorbent Assay; Risk Difference; Severe Acute Respiratory Syndrome Coronavirus 2; Kallikrein; Propensity Score Matching; Thrombin:Antithrombin; Von Willebrand Factor:Antigen; Carotid Artery Reactivity; Nod-like receptor family pyrin domain containing 3; alpha 1 antitrypsin; Confidence Interval; Endothelin-1
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2021.11.027

Endothelial damage and thrombosis caused by COVID-19 may imperil cardiovascular health. More than a year since the WHO declared COVID-19 pandemic, information on its effects beyond the acute phase is lacking. We investigate endothelial dysfunction, coagulation and inflammation, 3 months post-COVID-19. A cohort study was conducted including 203 patients with prior COVID-19. Macrovascular dysfunction was assessed by measuring the carotid artery diameter in response to hand immersion in ice-water. A historic cohort of 312 subjects served as controls. Propensity score matching corrected for baseline differences. Plasma concentrations of endothelin-1 were measured in patients post-COVID-19, during the acute phase, and in matched controls. Coagulation enzyme:inhibitor complexes and inflammatory cytokines were studied. The prevalence of macrovascular dysfunction did not differ between the COVID-19 (18.6%) and the historic cohort (22.5%, RD −4%, 95%CI: −15–7, p = 0.49). Endothelin-1 levels were significantly higher in acute COVID-19 (1.67 ± 0.64 pg/mL) as compared to controls (1.24 ± 0.37, p < 0.001), and further elevated 3 months post-COVID-19 (2.74 ± 1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16–30%. FVIIa:AT (35%) and Von Willebrand Factor:antigen (80.8%) were elevated. Inflammatory cytokine levels were high in a majority: interleukin(IL)-18 (73.9%), IL-6 (47.7%), and IL-1ra (48.9%). At 3 months after acute COVID-19 there was no indication of macrovascular dysfunction; there was evidence, however, of sustained endothelial cell involvement, coagulation activity and inflammation. Our data highlight the importance of further studies on SARS-CoV-2 related vascular inflammation and thrombosis, as well as longer follow-up in recovered patients. •No indication of macrovascular dysfunction 3 months after acute COVID-19•Elevated ET-1 levels during acute COVID-19, and further elevated after 3 months•Increased coagulation activity & high inflammatory cytokines 3 months post-COVID-19