Thromboinflammation in COVID-19: Can α₂ -macroglobulin help to control the fire?

The complex COVID-19-associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α₂ -macroglobulin (α₂ -M) levels from severe COVID-19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone- and protease-coated web-like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and "versatile" inhibitor α₂ -M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α₂ -M in COVID-19.