The complement system in COVID-19: friend and foe?

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.