Current medicinal chemistry · 2025
Role of Ferroptosis in the Progression of COVID-19 and the Development of Long COVID.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Zhao Wen, Wang Siyuan, Han Yuxin, Zhang Hongkun, Cao Jiacen, Dong Shasha, Li Dongdong, Lei Miao, Gao Yu, Liu Chuanmiao
Аннотация
OBJECTIVE: This study aimed to examine the role of ferroptosis on the pathogenesis and progression of COVID-19.
MATERIALS AND METHODS: A total of 127 patients who were hospitalized for COVID-19 were categorized into two groups according to the intensity of oxygen therapy (highflow or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one or two weeks after treatment. Telephone follow-up was performed 3 months after discharge to assess long COVID.
RESULTS: Patients receiving high-flow oxygen therapy had greater levels of neutrophils, D-dimer, C reactive protein, procalcitonin, plasma protein levels of tumor necrosis factor- alpha (TNF-α), interleukin 6 (IL-6), IL-17, acyl-CoA synthetase long-chain family member 4 (ACSL4), and PBMC mRNA level of TNF-α but had lower levels of lymphocytes and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and IL-17 and positive correlations of ACSL4 with inflammatory markers in plasma and PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower after treatment than at baseline, but there were higher post-treatment levels of lymphocytes, GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of plasma SLC7A11.
CONCLUSION: Ferroptosis is activated during the progression of COVID-19, and a low baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as a therapeutic target.
MATERIALS AND METHODS: A total of 127 patients who were hospitalized for COVID-19 were categorized into two groups according to the intensity of oxygen therapy (highflow or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one or two weeks after treatment. Telephone follow-up was performed 3 months after discharge to assess long COVID.
RESULTS: Patients receiving high-flow oxygen therapy had greater levels of neutrophils, D-dimer, C reactive protein, procalcitonin, plasma protein levels of tumor necrosis factor- alpha (TNF-α), interleukin 6 (IL-6), IL-17, acyl-CoA synthetase long-chain family member 4 (ACSL4), and PBMC mRNA level of TNF-α but had lower levels of lymphocytes and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and IL-17 and positive correlations of ACSL4 with inflammatory markers in plasma and PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower after treatment than at baseline, but there were higher post-treatment levels of lymphocytes, GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of plasma SLC7A11.
CONCLUSION: Ferroptosis is activated during the progression of COVID-19, and a low baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as a therapeutic target.