Published online Dec 26, 2022. doi: 10.12998/wjcc.v10.i36.13148
Peer-review started: July 20, 2022
First decision: November 5, 2022
Revised: November 20, 2022
Accepted: December 8, 2022
Article in press: December 8, 2022
Published online: December 26, 2022
Processing time: 159 Days and 13.2 Hours
Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.
Core Tip: Liver injury in patients with coronavirus disease 2019 (COVID-19) has progressively emerged, yet the exact pathophysiological mechanisms to explain liver pathogenicity is presently not fully understood. We hypothesize that cytokine storms caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may promote hyper-ferritinemia, which can further aggravate inflammation. Elevated ferritin levels can trigger nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, which leads to iron elevation, and ferroptosis. NCOA4-mediated ferritinophagy can be targeted to limit the ferroptosis and, therefore, prevent liver damage and disease severity in patients with COVID-19.