Severe COVID-19 is associated with hyperactivation of the alternative complement pathway

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Severe coronavirus disease 2019 (COVID-19) is linked to immune dysregulation, including impaired type I interferon activity and hyperinflammation.
• The complement system, a crucial part of innate immunity, is implicated in COVID-19 pathogenesis but its specific role remains unclear.

Purpose of the Study:

• To investigate the involvement of complement system pathways in severe COVID-19 at both the gene expression and protein levels.
• To characterize the contribution of the alternative complement pathway, for which data is limited, in severe COVID-19.

Main Methods:

• Systematic assessment of RNA levels for 28 complement genes in whole blood from COVID-19 patients and healthy controls.
• Analysis of gene expression patterns across different disease severities (moderate vs. severe/critical).
• Correlation of complement pathway activation markers with clinical parameters like inflammation and coagulopathy.

Main Results:

• Differential gene expression of complement system components was observed, varying with disease severity.
• Severe COVID-19 was associated with increased activation of the lectin and alternative complement pathways.
• Low properdin protein levels, despite high RNA expression, in severe/critical cases correlated significantly with mechanical ventilation requirement.

Conclusions:

• The alternative complement pathway plays a significant role in the pathogenesis of severe COVID-19.
• Properdin levels may serve as a biomarker for disease severity and the need for respiratory support.
• These findings support the investigation of therapeutic strategies targeting the alternative complement pathway for severe COVID-19 treatment.