ArticleFrontiers in immunology2020
Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key?
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Potential use of sodium glucose co-transporter 2 inhibitors during acute illness: a systematic review based on COVID-19.Endocrine · 2024Pooled it
- Intravenous lanadelumab for the treatment of moderately ill COVID-19 patients.British journal of clinical pharmacology · 2026Trial
- Article
- The combined manifestations of dramatically sore throat, congested and edematous mucosa, no-swelling tonsil are specific in acute Omicron pharyngitis.BMC infectious diseases · 2025Article
- Patterns of C1-Inhibitor Plasma Levels and Kinin-Kallikrein System Activation in Relation to COVID-19 Severity.Life (Basel, Switzerland) · 2024Article
- Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study.Biomedicines · 2024Article
- Aprotinin (I): Understanding the Role of Host Proteases in COVID-19 and the Importance of Pharmacologically Regulating Their Function.International journal of molecular sciences · 2024Review
- The Role of the Kinin System and the Effect of Des-ArginineInternational journal of molecular sciences · 2024Observational
- Potential Pathways and Pathophysiological Implications of Viral Infection-Driven Activation of Kallikrein-Kinin System (KKS).Viruses · 2024Review
- Macrophage Activation Syndrome in Coinciding Pandemics of Obesity and COVID-19: Worse than Bad.Advances in experimental medicine and biology · 2024Review
- Application of methylene blue for the prevention and treatment of COVID-19: A narrative review.Iranian journal of basic medical sciences · 2024Review
- Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective.Frontiers in immunology · 2024Article
- Prognostic Factors Associated with Acute Heart Failure in Patients Admitted for COVID-19: Analysis of the SEMI-COVID-19 Registry.Journal of clinical medicine · 2023Article
- Cell-Specific Mechanisms in the Heart of COVID-19 Patients.Circulation research · 2023Review
- Article
- Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression.Molecular immunology · 2022Review
- Understanding COVID-19-associated coagulopathy.Nature reviews. Immunology · 2022Review
- Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study.Research and practice in thrombosis and haemostasis · 2022Article
- The Role of Obesity, Body Composition, and Nutrition in COVID-19 Pandemia: A Narrative Review.Nutrients · 2022Review
- Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation.Nature reviews. Immunology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein-Kinin (KKS), the Coagulation/Fibrinolysis and the Renin-Angiotensin (RAS) Systems. We investigated the role of the mediators involved. CS consists of Factor XII (FXII) and plasma prekallikrein (complexed to high-molecular-weight kininogen-HK). Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK. BK binds to B2-receptors, mediating vascular permeability, vasodilation and edema. B1-receptors, binding the metabolite [des-Arg
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.