COVID-19: A case for plasma derived natural anticoagulants?

Area of Science:

• Biochemistry
• Immunology
• Hematology

Background:

• Convalescent plasma for COVID-19 passive immunization shows conflicting results.
• Severe COVID-19 is complicated by thromboinflammation, with limited efficacy of traditional anticoagulants.
• Key natural protease inhibitors (antithrombin III, α1-antitrypsin, α2-macroglobulin) are decreased in severe COVID-19 and influence prothrombotic and inflammatory pathways.

Purpose of the Study:

• To explore the potential of plasma proteins, beyond antibodies, for COVID-19 treatment.
• To investigate the role of natural protease inhibitors in COVID-19-associated thromboinflammation.
• To highlight the need for further research into the diagnostic, prognostic, and therapeutic applications of these inhibitors.

Main Methods:

• Review of existing literature on convalescent plasma, thromboinflammation, and protease inhibitors in COVID-19.
• Analysis of the roles of antithrombin III (ATIII), α1-antitrypsin (α1-AT), and α2-macroglobulin (α2-M) in COVID-19 pathophysiology.
• Comparison of the availability and therapeutic potential of different protease inhibitors.

Main Results:

• Conflicting evidence exists regarding the efficacy of convalescent plasma for COVID-19.
• Natural protease inhibitors (ATIII, α1-AT, α2-M) are reduced in severe COVID-19 and are critical in managing thromboinflammation.
• While ATIII and α1-AT are available as therapeutic concentrates, α2-M is not.

Conclusions:

• Plasma protease inhibitors represent a promising area for COVID-19 research and therapeutic development.
• Targeting thromboinflammation through protease inhibitors may offer an alternative or adjunct to antibody-based therapies.
• Further investigation into α2-macroglobulin and other protease inhibitors is crucial for clinical application.