Related Experiment Video
Updated: Dec 18, 2025
Depletion of Specific Cell Populations by Complement Depletion
Published on: February 5, 2010
The complement system in COVID-19: friend and foe?
Anuja Java1, Anthony J Apicelli2, M Kathryn Liszewski3
1Division of Nephrology.
Insights
Severe COVID-19 involves exaggerated immune responses, with complement activation playing a key role in disease severity. This suggests complement inhibitors could be a potential treatment for severe coronavirus disease 2019.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health crisis.
- Exaggerated immune responses contribute to COVID-19 morbidity and mortality.
- The complement system's role in COVID-19 severity is increasingly recognized.
Purpose of the Study:
- To summarize current knowledge on coronavirus interactions with the complement system.
- To explore the link between complement activation and COVID-19 severity.
- To provide a basis for clinical trials of complement inhibitors.
Main Methods:
- Review of current scientific literature on coronaviruses and the complement system.
- Analysis of clinical features of severe COVID-19 in relation to complementopathies.
- Synthesis of evidence linking complement activation, neutrophilia, endothelial injury, and hypercoagulability.
Main Results:
- Coronaviruses activate multiple complement pathways.
- Severe COVID-19 clinical manifestations resemble complement-mediated disorders (complementopathies).
- Complement activation, neutrophilia, endothelial injury, and hypercoagulability are intertwined in severe COVID-19.
Conclusions:
- A subset of COVID-19 patients may have a genetic predisposition to complement dysregulation.
- Complement activation is a significant driver of severe COVID-19.
- Complement inhibitors represent a promising therapeutic strategy for life-threatening COVID-19.
Abstract:
Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.
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