ArticleeLife2020
Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04632732 (Apelin; ACE2 and Biomarkers of Alveolar-capillary Permeability in SARS-cov-2), which is not on this map. Cited by 194 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Apelin; ACE2 and Biomarkers of Alveolar-capillary Permeability in SARS-cov-2 (COVID-19).
Who cites it
194 citing papers in PubMed, 4 syntheses or guidelines pooled it, 302 citations in OpenAlex.
- Pooled it
- SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.The Cochrane database of systematic reviews · 2021Pooled it
- COVID-19, corticosteroids and public health: a reappraisal.Public health · 2021Pooled it
- A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Pooled 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
- Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- COVID-19 as a trigger of acute attacks in people with hereditary angioedema.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2021Trial
- Targeting the NLRP3 Inflammasome with Colchicine in COVID-19: Therapeutic Evidence and Future Implications for Influenza.International journal of molecular sciences · 2026Review
- Therapeutic Targeting of the Bradykinin B2 Receptor in Immunological and Vascular Diseases: Insights from Kinin Biology to Clinical Outcomes.Clinical reviews in allergy & immunology · 2026Review
- Proteomic Analysis of Cerebrospinal Fluid from Severe COVID-19 Patients Reveals Prognostic Biomarkers Associated with Disease Outcome.Proteomics. Clinical applications · 2026Article
- The immunomodulatory potential of bradykinin signaling in autoimmune conditions.Frontiers in immunology · 2026Review
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- Insights from the Evolution of Coagulation: A New Perspective on Anti-Inflammatory Strategies in the ICU-Focus on the Contact Activation System.Biomedicines · 2025Review
- Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?International journal of molecular sciences · 2025Review
- Review
- Patterns of C1-Inhibitor Plasma Levels and Kinin-Kallikrein System Activation in Relation to COVID-19 Severity.Life (Basel, Switzerland) · 2024Article
- The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19.International journal of molecular sciences · 2024Review
- 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
- Safety of High-Dose Vitamin C in Non-Intensive Care Hospitalized Patients with COVID-19: An Open-Label Clinical Study.Journal of clinical medicine · 2024Article
134 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents.
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What OpenQuestion holds
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.