Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19...

Area of Science:

• Immunology
• Complement System
• Pathophysiology

Background:

• The innate immune response to SARS-CoV-2 involves complement activation, which can lead to tissue damage.
• Complement regulatory proteins, such as CR1, play a crucial role in controlling complement-mediated inflammation.
• Erythrocytes (E) can be involved in immune processes, including the deposition of complement fragments.

Purpose of the Study:

• To investigate the role of complement activation and regulatory proteins in COVID-19 pathophysiology.
• To assess CR1 density, C4d deposits, and C3b/C3bi products on erythrocytes in COVID-19 patients.
• To explore potential diagnostic or therapeutic implications of these findings.

Main Methods:

• Studied 52 COVID-19 patients in ICU units receiving oxygen therapy or mechanical ventilation.
• Assessed CR1 density on erythrocytes (E) using flow cytometry.
• Measured C4d and C3 deposits on erythrocytes via immunofluorescence.

Main Results:

• COVID-19 patients exhibited significantly decreased CR1 density on E compared to healthy individuals (p < 10^-6).
• Over 80% of patients showed large C4d deposits on E, often without concomitant C3 deposits.
• Decreased CR1 density correlated with clinical severity and fatal outcomes.

Conclusions:

• Reduced CR1 density and increased C4d deposits on erythrocytes suggest significant complement activation in COVID-19.
• Erythrocytes appear to play a role in the immune pathophysiology of SARS-CoV-2 infection.
• CR1 density and C4d deposits on E may serve as biomarkers for disease monitoring and suggest CR1-based therapies.