Protease inhibitor plasma concentrations associate with COVID-19 infection

Area of Science:

• Immunology
• Proteomics
• Nephrology

Background:

• Protease inhibitors are crucial in regulating innate immunity and inflammation.
• Chronic haemodialysis patients represent a vulnerable population for severe COVID-19 outcomes.
• Understanding early immune markers in COVID-19 is vital for predicting disease severity.

Purpose of the Study:

• To quantify plasma concentrations of anti-inflammatory protease inhibitors in haemodialysis patients with COVID-19.
• To investigate the association between protease inhibitor levels and COVID-19 presence and severity.
• To establish early disease markers for COVID-19 in this patient cohort.

Main Methods:

• Utilized antibody-based immunoassays to measure plasma levels of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin, and inter-alpha-inhibitor heavy chain 4 (ITIH4).
• Analyzed 100 serial samples from 27 haemodialysis patients with COVID-19, compared with 32 haemodialysis controls and 32 healthy controls.
• Assessed ITIH4 in both intact and total forms, correlating levels with COVID-19 severity and C-reactive protein.

Main Results:

• COVID-19 patients showed lower plasma C1 esterase inhibitor and alpha2-macroglobulin, and higher total ITIH4 compared to dialysis controls.
• These alterations were evident in samples collected as early as 4 days post-diagnosis.
• Elevated plasma ITIH4 levels correlated with more severe COVID-19 cases.
• Serum C-reactive protein positively correlated with antithrombin, intact ITIH4, and total ITIH4.

Conclusions:

• Plasma protease inhibitor concentrations are significantly altered in COVID-19 patients undergoing chronic haemodialysis.
• Early detection of these changes may serve as potential biomarkers for disease severity.
• Further research is warranted to explore the therapeutic implications of these findings.