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

L.H. Willems; M. Nagy; H. Ten Cate; H.M.H. Spronk; L.A. Groh; J. Leentjens; N.A.F. Janssen; M.G. Netea; D.H.J. Thijssen; G. Hannink; A.S. van Petersen; M.C. Warle

doi:10.1016/j.thromres.2021.11.027

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

L.H. Willems, M. Nagy, H. Ten Cate, H.M.H. Spronk, L.A. Groh, J. Leentjens, N.A.F. Janssen, M.G. Netea, D.H.J. Thijssen, G. Hannink, A.S. van Petersen, M.C. Warle^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Introduction: 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.& nbsp;Materials and methods: 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.& nbsp;Results and conclusions: 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 +/-& nbsp;1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16-30%. FVII: 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.

Original language	English
Pages (from-to)	106-114
Number of pages	9
Journal	Thrombosis Research
Volume	209
DOIs	https://doi.org/10.1016/j.thromres.2021.11.027
Publication status	Published - 1 Jan 2022

Keywords

Blood coagulation
COVID-19
DISEASE
Endothelial cells
Inflammation
MECHANISMS
RELAXATION
SARS-CoV-2
SYSTEM
THROMBIN

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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., & Warle, M. C. (2022). Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19. Thrombosis Research, 209, 106-114. https://doi.org/10.1016/j.thromres.2021.11.027

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

abstract = "Introduction: 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.& nbsp;Materials and methods: 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.& nbsp;Results and conclusions: 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 +/-& nbsp;1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16-30%. FVII: 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.",

keywords = "Blood coagulation, COVID-19, DISEASE, Endothelial cells, Inflammation, MECHANISMS, RELAXATION, SARS-CoV-2, SYSTEM, THROMBIN",

author = "L.H. Willems and M. Nagy and {Ten Cate}, H. and H.M.H. Spronk and L.A. Groh and J. Leentjens and N.A.F. Janssen and M.G. Netea and D.H.J. Thijssen and G. Hannink and {van Petersen}, A.S. and M.C. Warle",

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doi = "10.1016/j.thromres.2021.11.027",

language = "English",

volume = "209",

pages = "106--114",

journal = "Thrombosis Research",

issn = "0049-3848",

publisher = "Elsevier Science",

}

Willems, LH, Nagy, M , Ten Cate, H , Spronk, HMH, Groh, LA, Leentjens, J, Janssen, NAF, Netea, MG, Thijssen, DHJ, Hannink, G, van Petersen, AS & Warle, MC 2022, 'Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19', Thrombosis Research, vol. 209, pp. 106-114. https://doi.org/10.1016/j.thromres.2021.11.027

TY - JOUR

T1 - Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19

AU - Willems, L.H.

AU - Nagy, M.

AU - Ten Cate, H.

AU - Spronk, H.M.H.

AU - Groh, L.A.

AU - Leentjens, J.

AU - Janssen, N.A.F.

AU - Netea, M.G.

AU - Thijssen, D.H.J.

AU - Hannink, G.

AU - van Petersen, A.S.

AU - Warle, M.C.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Introduction: 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.& nbsp;Materials and methods: 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.& nbsp;Results and conclusions: 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 +/-& nbsp;1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16-30%. FVII: 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.

AB - Introduction: 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.& nbsp;Materials and methods: 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.& nbsp;Results and conclusions: 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 +/-& nbsp;1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16-30%. FVII: 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.

KW - Blood coagulation

KW - COVID-19

KW - DISEASE

KW - Endothelial cells

KW - Inflammation

KW - MECHANISMS

KW - RELAXATION

KW - SARS-CoV-2

KW - SYSTEM

KW - THROMBIN

U2 - 10.1016/j.thromres.2021.11.027

DO - 10.1016/j.thromres.2021.11.027

M3 - Article

C2 - 34922160

SN - 0049-3848

VL - 209

SP - 106

EP - 114

JO - Thrombosis Research

JF - Thrombosis Research

ER -

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

Abstract

Keywords

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