Figure 1.

Schematic diagram of spiraled inflammatory activation and tissue damage by hemolysis in severe COVID-19. Sepsis causes intravascular hemolysis by many mechanisms (e.g., microvasculitis, complement activation, glucose metabolism, and eryptosis), leading to increased vascular permeability, and thereby extravasation of both red blood cells and immune system cells. The first target in the proposed treatment strategy is a decrease in intravascular hemolysis. In terms of the alveolar microenvironment, increases in extravasated cells, cytokines, and metal ions deteriorate hemolysis in the extracellular space, which is associated with spiraled inflammatory activation in lung issue. Therefore, the second therapeutic target is a decrease in extravascular hemolysis. (This figure was created at BioRender.com.).