SARS-CoV-2 induces ferroptosis through multiple mechanisms, thereby enhancing its pathogenicity. In sinoatrial node cell lines, infection triggers ferroptosis. While in ischemic stroke, ACSL4 esterification promotes ferroptosis. The SARS-CoV-2 Orf 7b protein mediates ferroptosis via c-Myc, leading to lung injury. Additionally, ORF 3a sensitizes cells to ferroptosis through the Keap1-NRF2 axis. ORF 3a stabilizes Keap1, which promotes NRF2 degradation and relieves the inhibition of ferroptosis. This evidence concerns the gene NFE2L2 and infection.