Fig. 1: SARS-CoV-2, Multiple Organ Failure and the Possible Triggering of Ferroptosis.

A Schematic representation of SARS-CoV-2 causing multiple organ failure (MOF). SARS-CoV-2 recognizes the AEC2 receptor in the alveoli, especially the type II alveolar cells (AT2). This infection triggers the immune response and inflammation, causing damage to the blood-air barrier. In this case, SARS-CoV-2 therefore passes through the barrier, reaching to the capillaries and continues recognizing the ACE2 located in the different organs within the blood circulation. As a result, organs expressed with ACE2 may get infected and damaged by the activated immune system, thereby causing the MOF. B A hypothesis of how SARS-CoV-2 may trigger ferroptosis. After incubation period, the invading SARS-CoV-2 causes cytotoxic effect to multiple organs. Due to the infection, a plethora of transferrins carrying with Fe³⁺ are recognized by transferrin receptors thereby entering into the cell. Then, divalent metal transporter 1 (DMT1) transformed Fe³⁺ to Fe²⁺, accompanied with iron accumulation in the cell. Hydrogen peroxide (H₂O₂), Fe²⁺, and lipid together cause Fenton reaction, producing massive lipid reactive oxygen species (ROS). This can be eliminated by glutathione (GSH) with the help of Glutathione peroxidase 4 (GPX4). However, owing to the iron overload, extensive Fention reaction would generate a large number of lipid ROS, causing cell membrane damage.