SARS-CoV-2 Triggers Complement Activation through Interactions with Heparan Sulfate
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
The complement system has been heavily implicated in severe COVID-19 with clinical studies revealing widespread gene induction, deposition, and activation. However, the mechanism by which complement is activated in this disease remains incompletely understood. Herein we examined the relationship between SARS-CoV-2 and complement by inoculating the virus in lepirudin-anticoagulated human blood. This caused progressive C5a production after 30 minutes and 24 hours, which was blocked entirely 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 deposition of complement and interactions with heparan sulfate. Additional functional analysis revealed that complement-dependent granulocyte and monocyte activation was delayed. Indeed, C5aR1 internalisation and CD11b upregulation on these cells only occurred after 24 hours. Thus, SARS-CoV-2 is a non-canonical complement activator that triggers the alternative pathway through interactions with heparan sulfate.
Article activity feed
-
SciScore for 10.1101/2022.01.11.475820: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study approval: This research was approved by the University of Queensland Human Research Ethics Committee and the University of Queensland Biosafety Committee (supplementary methods 1).
Consent: All participants gave informed written consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data analysis was performed with FlowJo v10.6.2. FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical analysis: Statistical analysis was performed with GraphPad Prism Software v9.3.1. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect …
SciScore for 10.1101/2022.01.11.475820: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study approval: This research was approved by the University of Queensland Human Research Ethics Committee and the University of Queensland Biosafety Committee (supplementary methods 1).
Consent: All participants gave informed written consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data analysis was performed with FlowJo v10.6.2. FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical analysis: Statistical analysis was performed with GraphPad Prism Software v9.3.1. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
-