Here, we speculate on the presence of the following defensive mechanisms that could occur against free iron/heme toxicity and oxidative stress during COVID-19: (i) Tf, Cp, and LCN2 are increased to protect against free iron by reducing Fe3+; (ii) the antioxidant enzyme SOD1 is upregulated to reduce ROS levels and modulate LCN2 levels; (iii) HPX protein levels are enhanced to protect against free heme toxicity and prevent further hemolysis (Figure 5). Here, HPX is linked to COVID-19.