SARS-CoV-2 triggers complement activation through interactions with heparan sulfate
Research article published in Clinical & translational immunology (2022)
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
To determine whether SARS-CoV-2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect.
Por qué esto importa para la hirudoterapia
This study investigated whether SARS-CoV-2 triggers complement activation using a human lepirudin-anticoagulated whole blood model, finding that the virus progressively activates the alternative complement pathway through interactions with cell-surface heparan sulfate, leading to C5a production and downstream leukocyte signaling. Lepirudin, a recombinant hirudin, is mentioned solely as the anticoagulant reagent used in the ex vivo blood model and is not itself the subject of investigation. The study's focus is viral immunology and complement biology. The connection to ASH's domain is minimal: lepirudin serves only as an experimental tool, and the study provides no data relevant to hirudotherapy, leech biology, or the therapeutic properties of the leech secretome.
Citación
SARS-CoV-2 triggers complement activation through interactions with heparan sulfate
Lo MW et al. · Clinical & translational immunology, 2022
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026