Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients

Area of Science:

• Immunology
• Virology
• Pathophysiology

Background:

• Coronavirus disease 19 (COVID-19) can manifest as a multi-organ illness with hyperinflammation and prothrombotic states, known as immunothrombosis.
• Complement activation has been implicated in severe COVID-19 and immunothrombosis.

Purpose of the Study:

• To investigate complement system involvement in the early stages of COVID-19.
• To determine if complement activation can predict negative disease outcomes.

Main Methods:

• Symptomatic SARS-CoV-2 positive patients (n=97) were assessed upon emergency room presentation.
• Plasma levels of soluble C5b-9 (sC5b-9) and C5a were measured using ELISA.
• Serum mediators, including cytokines and VEGF factors, and routine laboratory parameters were analyzed.

Main Results:

• Hospitalized patients (moderate/severe COVID-19) showed significantly increased sC5b-9 and C5a levels compared to mild, non-hospitalized patients.
• Elevated sC5b-9 and C5a levels predicted disease severity at 4-week follow-up.
• Complement activation was observed even in mild cases and correlated with inflammatory markers like CRP and ferritin.

Conclusions:

• The complement system is activated early in COVID-19, irrespective of symptom severity.
• Complement activation is an early predictor of negative outcomes in COVID-19 patients.
• Early complement involvement may occur independently of significant pro-inflammatory cytokine elevation.