ArticleFrontiers in immunology2021
SARS-CoV-2 Exacerbates COVID-19 Pathology Through Activation of the Complement and Kinin Systems.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The rationale for the treatment of long-Covid symptoms - A cardiologist's view.Frontiers in cardiovascular medicine · 2022Pooled it
- 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
- 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
- Transcriptomic analysis of differential expression between surviving and nonsurviving patients infected by the SARS-CoV-2 Delta variant.Scientific reports · 2025Article
- Article
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- Enhanced complement activation and MAC formation accelerates severe COVID-19.Cellular and molecular life sciences : CMLS · 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
- SARS-CoV-2 Nucleocapsid Protein Is Not Responsible for Over-Activation of Complement Lectin Pathway.International journal of molecular sciences · 2024Article
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.Molecular systems biology · 2024Article
- Emerging role of complement in COVID-19 and other respiratory virus diseases.Cellular and molecular life sciences : CMLS · 2024Review
- 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
- COVID-19: Not a thrombotic disease but a thromboinflammatory disease.Upsala journal of medical sciences · 2024Review
- Article
- Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective.Frontiers in immunology · 2024Article
- Macrophage Activation Syndrome in Coinciding Pandemics of Obesity and COVID-19: Worse than Bad.Advances in experimental medicine and biology · 2024Review
- Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Infection with SARS-CoV-2 triggers the simultaneous activation of innate inflammatory pathways including the complement system and the kallikrein-kinin system (KKS) generating in the process potent vasoactive peptides that contribute to severe acute respiratory syndrome (SARS) and multi-organ failure. The genome of SARS-CoV-2 encodes four major structural proteins - the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein. However, the role of these proteins in either binding to or activation of the complement system and/or the KKS is still incompletely understood. In these studies, we used: solid phase ELISA, hemolytic assay and surface plasmon resonance (SPR) techniques to examine if recombinant proteins corresponding to S1, N, M and E: (a) bind to C1q, gC1qR, FXII and high molecular weight kininogen (HK), and (b) activate complement and/or the KKS. Our data show that the viral proteins: (a) bind C1q and activate the classical pathway of complement, (b) bind FXII and HK, and activate the KKS in normal human plasma to generate bradykinin and (c) bind to gC1qR, the receptor for the globular heads of C1q (gC1q) which in turn could serve as a platform for the activation of both the complement system and KKS. Collectively, our data indicate that the SARS-CoV-2 viral particle can independently activate major innate inflammatory pathways for maximal damage and efficiency. Therefore, if efficient therapeutic modalities for the treatment of COVID-19 are to be designed, a strategy that includes blockade of the four major structural proteins may provide the best option.
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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.