Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity

Area of Science:

• Immunology
• Biochemistry

Background:

• Innate immunity investigations often rely on static measurements, potentially misrepresenting protein function.
• Protein function is complex, influenced by interconnected pathways and feedback regulation, necessitating functional analysis over static abundance.

Purpose of the Study:

• To investigate innate immunity protein function in COVID-19 patients using functional mass spectrometry.
• To measure anti-protease and complement activity in COVID-19 patient plasma and correlate with disease severity.

Main Methods:

• Functional mass spectrometry was employed to assess plasma anti-protease and complement activity.
• Measurements included neutrophil elastase, granzyme B, alpha-1 antitrypsin (AAT), alpha-1-antichymotrypsin (ACT), and C3a/C3beta ratios.

Main Results:

• COVID-19 patients exhibited a protease storm with elevated neutrophil elastase and granzyme B within 48 hours of admission.
• Anti-protease activity (AAT, ACT) significantly increased, balancing protease activity.
• Decreased C3a/C3beta ratio indicated increased complement activation, correlating with COVID-19 severity.
• AAT, ACT, and C3a/C3beta levels remained stable over 10 hospital days.

Conclusions:

• COVID-19 is characterized by a protease storm and complement activation, with protease activity partially counteracted by enhanced anti-protease function.
• The AAT/ACT and C3a/C3beta ratios serve as indicators of neutrophil elastase neutralization and complement activation, respectively, reflecting COVID-19 severity.