Observational studyFrontiers in immunology2022
Impaired Kallikrein-Kinin System in COVID-19 Patients' Severity.
Observational study in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A systematic review of the measurement of the renin-angiotensin and kallikrein-kinin system peptides in normotension and hypertension.Journal of human hypertension · 2026Pooled it
- Intravenous lanadelumab for the treatment of moderately ill COVID-19 patients.British journal of clinical pharmacology · 2026Trial
- Pathophysiology of COVID-19: A Post Hoc Analysis of the ICAT-COVID Clinical Trial of the Bradykinin Antagonist Icatibant.Pathogens (Basel, Switzerland) · 2025Trial
- Article
- SARS-Cov-2 Replication in a Blood-Brain Barrier Model Established with Human Brain Microvascular Endothelial Cells Induces Permeability and Disables ACE2-Dependent Regulation of Bradykinin B1 Receptor.International journal of molecular sciences · 2025Article
- Treatment with intravenous immunoglobulin modulates coagulation- and complement-related pathways in COVID-19 patients.Frontiers in immunology · 2025Article
- Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.Cardiovascular diabetology · 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
- Levels of Angiotensin and Kinin Metabolite Peptides Related to COVID-19 Severity.ACS pharmacology & translational science · 2024Article
- A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection.European journal of human genetics : EJHG · 2024Review
- Subtyping of COVID-19 samples based on cell-cell interaction in single cell transcriptomes.Scientific reports · 2023Article
- Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond.Frontiers in physiology · 2023Review
- Upregulation of miRNA-200c during Disease Progression in COVID-19 Patients.Journal of clinical medicine · 2022Article
- Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression.Molecular immunology · 2022Review
- Immune response induced by novel coronavirus infection.Frontiers in cellular and infection microbiology · 2022Review
- The des-ArgFrontiers in physiology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COVID-19 has emerged as a devastating disease in the last 2 years. Many authors appointed to the importance of kallikrein-kinin system (KKS) in COVID-19 pathophysiology as it is involved in inflammation, vascular homeostasis, and coagulation. We aim to study the bradykinin cascade and its involvement in severity of patients with COVID-19. This is an observational cohort study involving 63 consecutive patients with severe COVID-19 pneumonia and 27 healthy subjects as control group. Clinical laboratory findings and plasma protein concentration of KKS peptides [bradykinin (BK), BK1-8], KKS proteins [high-molecular weight kininogen (HK)], and KKS enzymes [carboxypeptidase N subunit 1 (CPN1), kallikrein B1 (KLKB1), angiotensin converting enzyme 2 (ACE2), and C1 esterase inhibitor (C1INH)] were analyzed. We detected dysregulated KKS in patients with COVID-19, characterized by an accumulation of BK1-8 in combination with decreased levels of BK. Accumulated BK1-8 was related to severity of patients with COVID-19. A multivariate logistic regression model retained BK1-8, BK, and D-dimer as independent predictor factors to intensive care unit (ICU) admission. A Youden's optimal cutoff value of -0.352 was found for the multivariate model score with an accuracy of 92.9%. Multivariate model score-high group presented an odds ratio for ICU admission of 260.0. BK1-8 was related to inflammation, coagulation, and lymphopenia. Our data suggest that BK1-8/BK plasma concentration in combination with D-dimer levels might be retained as independent predictors for ICU admission in patients with COVID-19. Moreover, we reported KKS dysregulation in patients with COVID-19, which was related to disease severity by means of inflammation, hypercoagulation, and lymphopenia.
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