ArticleClinical & translational immunology2022
SARS-CoV-2 triggers complement activation through interactions with heparan sulfate.
Article in Clinical & translational immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Impact of complement system proteins on the clinical progression of hospitalized patients with COVID-19.BMC infectious diseases · 2025Article
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies.The EMBO journal · 2024Article
- Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.Frontiers in immunology · 2024Observational
- Understanding COVID-19-associated endothelial dysfunction: role of PIEZO1 as a potential therapeutic target.Frontiers in immunology · 2024Review
- Molecular interactions between perlecan LG3 and the SARS-CoV-2 spike protein receptor binding domain.Protein science : a publication of the Protein Society · 2024Article
- Global impact of proteoglycan science on human diseases.iScience · 2023Review
- Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies.Current issues in molecular biology · 2023Review
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objectives: To determine whether SARS-CoV-2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect. Methods: SARS-CoV-2 was inoculated into a human lepirudin-anticoagulated whole blood model, which contains a full repertoire of complement factors and leukocytes that express complement receptors. Complement activation was determined by measuring C5a production with an ELISA, and pretreatment with specific inhibitors was used to identify the pathways involved. The functional significance of this was then assessed by measuring markers of C5a signalling including leukocyte C5aR1 internalisation and CD11b upregulation with flow cytometry. Results: SARS-CoV-2 inoculation in this whole blood model caused progressive C5a production over 24 h, which was significantly reduced by inhibitors for factor B, C3, C5 and heparan sulfate. However, this phenomenon could not be replicated in cell-free plasma, highlighting the requirement for cell surface interactions with heparan sulfate. Functional analysis of this phenomenon revealed that C5aR1 signalling and CD11b upregulation in granulocytes and monocytes was delayed and only occurred after 24 h. Conclusion: SARS-CoV-2 is a noncanonical alternative pathway activator that progressively triggers complement activation through interactions with heparan sulfate.
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