Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review

Gianni, Panagiota; Goldin, Mark; Ngu, Sam; Zafeiropoulos, Stefanos; Geropoulos, Georgios; Giannis, Dimitrios

doi:10.5493/wjem.v12.i4.53

Cited by 13 publications

(12 citation statements)

References 116 publications

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“…First, SARS-CoV2 interacts with the angiotensin converting enzyme (ACE)-2 receptor on endothelial cells, which results in an increased release of the vasoconstrictor angiotensin-II and an endothelial dysfunction [ 158 ]. In addition, inflammatory response plays a primary role through complement activation, elevating levels of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-17A, which activate platelets, tissue factor and then the coagulation cascade [ 159 , 160 ]. Moreover, recent studies have shown alterations of both coagulation and fibrinolysis by multiple pathways, such as reduction of antithrombin and protein C and increasing of PAI-1 [ 160 , 161 ].…”

Section: Risk Factors For Venous Thromboembolismmentioning

confidence: 99%

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

Pastori

Cormaci

Marucci

et al. 2023

IJMS

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Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

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Section: Risk Factors For Venous Thromboembolismmentioning

confidence: 99%

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

Pastori

Cormaci

Marucci

et al. 2023

IJMS

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“…Endothelial activation and innate immune system recruitment promote and stimulate the initiation of a procoagulant state, so-called immunothrombosis. 6,55,56 While the concept of a specific interaction between inflammatory processes with pro-coagulative mechanisms has been previously described, including general ARDS and sepsis which is not unique to COVID-19associated vasculopathies, immunothrombosis is considered as a pathologic key mechanism in the formation of microthrombi in COVID-19. 7,[57][58][59][60] Besides immunothrombosis, which defines a specific response of the innate immune system together with the coagulation system to destroy pathogens and restrict their dissemination, another term, called thromboinflammation, is also frequently used to describe the sole concomitance of inflammation and thrombosis.…”

Section: Immunothrombosismentioning

confidence: 99%

Pathophysiological Aspects of COVID-19-Associated Vasculopathic Diseases

Greistorfer,

Jud

2023

Thromb Haemost

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Since the beginning of coronavirus disease 2019 (COVID-19) pandemic, numerous data reported potential effects on the cardiovascular system due to infection by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which may lead to COVID-19-associated vasculopathies during the acute phase and measurable vascular changes in the convalescent phase. Infection by SARS-CoV-2 seems to have specific direct and indirect effects on the endothelium, immune and coagulation systems thus promoting endothelial dysfunction, immunothrombosis, and formation of neutrophil extracellular traps although the exact mechanisms still need to be elucidated. This review represents a recent update of pathophysiological pathways of the respective three major mechanisms contributing to COVID-19 vasculopathies and vascular changes and includes clinical implications and significance of outcome data.

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Section: Biological Mechanisms For In Situ Pulmonary Immunothrombosismentioning

confidence: 99%

“…The complement system is a key mediator of the innate immune response and inflammation [ 84 ]. Lectin and alternative pathways mediate complement activation by SARS-CoV-2 S and N proteins [ 85 , 86 , 87 ], which will lead to EC and MC degranulation, enhanced phagocytic activity of neutrophils and monocytes, and “orchestration” of a proinflammatory environment [ 84 ]. Cleavage components C3a and C5a are potent inflammatory molecules capable of inducing the release of proinflammatory cytokines as part of the COVID-19-associated “cytokine storm” [ 87 ].…”

Section: Biological Mechanisms For In Situ Pulmonary Immunothrombosismentioning

confidence: 99%

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Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

2023

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COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation–endotheliopathy–thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.

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Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review

Cited by 13 publications

References 116 publications

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

Pathophysiological Aspects of COVID-19-Associated Vasculopathic Diseases

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

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