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World J Clin Cases. Dec 26, 2022; 10(36): 13148-13156
Published online Dec 26, 2022. doi: 10.12998/wjcc.v10.i36.13148
Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable
Feng-Ju Jia, Jing Han
Feng-Ju Jia, Jing Han, School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
Author contributions: Jia FJ designed and wrote the manuscript; Han J revised the manuscript; All authors have read and approve the final manuscript.
Supported by Shandong Provincial Natural Science Foundation, No. ZR2020QC088.
Conflict-of-interest statement: All the Author report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng-Ju Jia, PhD, Doctor, School of Nursing, Qingdao University, No. 308 Ningxia Road, Qingdao 266071, Shandong Province, China. jiafegngjv@163.com
Received: July 20, 2022
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
Abstract

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.

Keywords: COVID-19, Liver injury, Ferritinophagy, Ferroptosis, Iron, SARS-CoV-2

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.