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Ferroptosis and pyroptosis signatures in critical COVID-19 patients

Cédric Peleman, Samya Van Coillie, Symen Ligthart, Sze Men Choi (UGent) , Jan De Waele (UGent) , Pieter Depuydt (UGent) , Dominique Benoit (UGent) , HANNAH SCHAUBROECK (UGent) , Sven M. Francque, Karolien Dams, et al.
(2023) CELL DEATH AND DIFFERENTIATION. 30(9). p.2066-2077
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Abstract
Critical COVID-19 patients admitted to the intensive care unit (ICU) frequently suffer from severe multiple organ dysfunction with underlying widespread cell death. Ferroptosis and pyroptosis are two detrimental forms of regulated cell death that could constitute new therapeutic targets. We enrolled 120 critical COVID-19 patients in a two-center prospective cohort study to monitor systemic markers of ferroptosis, iron dyshomeostasis, pyroptosis, pneumocyte cell death and cell damage on the first three consecutive days after ICU admission. Plasma of 20 post-operative ICU patients (PO) and 39 healthy controls (HC) without organ failure served as controls. Subsets of COVID-19 patients displayed increases in individual biomarkers compared to controls. Unsupervised clustering was used to discern latent clusters of COVID-19 patients based on biomarker profiles. Pyroptosis-related interleukin-18 accompanied by high pneumocyte cell death was independently associated with higher odds at mechanical ventilation, while the subgroup with high interleuking-1 beta (but limited pneumocyte cell death) displayed reduced odds at mechanical ventilation and lower mortality hazard. Meanwhile, iron dyshomeostasis with a tendency towards higher ferroptosis marker malondialdehyde had no association with outcome, except for the small subset of patients with very high catalytic iron independently associated with reduced survival. Forty percent of patients did not have a clear signature of the cell death mechanisms studied in this cohort. Moreover, repeated moderate levels of soluble receptor of advanced glycation end products and growth differentiation factor 15 during the first three days after ICU admission are independently associated with adverse clinical outcome compared to sustained lower levels. Altogether, the data point towards distinct subgroups in this cohort of critical COVID-19 patients with different systemic signatures of pyroptosis, iron dyshomeostasis, ferroptosis or pneumocyte cell death markers that have different outcomes in ICU. The distinct groups may allow 'personalized' treatment allocation in critical COVID-19 based on systemic biomarker profiles.
Keywords
Cell Biology, Molecular Biology

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MLA
Peleman, Cédric, et al. “Ferroptosis and Pyroptosis Signatures in Critical COVID-19 Patients.” CELL DEATH AND DIFFERENTIATION, vol. 30, no. 9, Springer Science and Business Media LLC, 2023, pp. 2066–77, doi:10.1038/s41418-023-01204-2.
APA
Peleman, C., Van Coillie, S., Ligthart, S., Choi, S. M., De Waele, J., Depuydt, P., … Vanden Berghe, T. (2023). Ferroptosis and pyroptosis signatures in critical COVID-19 patients. CELL DEATH AND DIFFERENTIATION, 30(9), 2066–2077. https://doi.org/10.1038/s41418-023-01204-2
Chicago author-date
Peleman, Cédric, Samya Van Coillie, Symen Ligthart, Sze Men Choi, Jan De Waele, Pieter Depuydt, Dominique Benoit, et al. 2023. “Ferroptosis and Pyroptosis Signatures in Critical COVID-19 Patients.” CELL DEATH AND DIFFERENTIATION 30 (9): 2066–77. https://doi.org/10.1038/s41418-023-01204-2.
Chicago author-date (all authors)
Peleman, Cédric, Samya Van Coillie, Symen Ligthart, Sze Men Choi, Jan De Waele, Pieter Depuydt, Dominique Benoit, HANNAH SCHAUBROECK, Sven M. Francque, Karolien Dams, Rita Jacobs, Dominique Robert, Ria Roelandt, Ruth Seurinck, Yvan Saeys, Mohan Rajapurkar, Philippe G. Jorens, Eric Hoste, and Tom Vanden Berghe. 2023. “Ferroptosis and Pyroptosis Signatures in Critical COVID-19 Patients.” CELL DEATH AND DIFFERENTIATION 30 (9): 2066–2077. doi:10.1038/s41418-023-01204-2.
Vancouver
1.
Peleman C, Van Coillie S, Ligthart S, Choi SM, De Waele J, Depuydt P, et al. Ferroptosis and pyroptosis signatures in critical COVID-19 patients. CELL DEATH AND DIFFERENTIATION. 2023;30(9):2066–77.
IEEE
[1]
C. Peleman et al., “Ferroptosis and pyroptosis signatures in critical COVID-19 patients,” CELL DEATH AND DIFFERENTIATION, vol. 30, no. 9, pp. 2066–2077, 2023.
@article{01H936GZXPY5GHBHP5JSSNF7H4,
  abstract     = {{Critical COVID-19 patients admitted to the intensive care unit (ICU) frequently suffer from severe multiple organ dysfunction with underlying widespread cell death. Ferroptosis and pyroptosis are two detrimental forms of regulated cell death that could constitute new therapeutic targets. We enrolled 120 critical COVID-19 patients in a two-center prospective cohort study to monitor systemic markers of ferroptosis, iron dyshomeostasis, pyroptosis, pneumocyte cell death and cell damage on the first three consecutive days after ICU admission. Plasma of 20 post-operative ICU patients (PO) and 39 healthy controls (HC) without organ failure served as controls. Subsets of COVID-19 patients displayed increases in individual biomarkers compared to controls. Unsupervised clustering was used to discern latent clusters of COVID-19 patients based on biomarker profiles. Pyroptosis-related interleukin-18 accompanied by high pneumocyte cell death was independently associated with higher odds at mechanical ventilation, while the subgroup with high interleuking-1 beta (but limited pneumocyte cell death) displayed reduced odds at mechanical ventilation and lower mortality hazard. Meanwhile, iron dyshomeostasis with a tendency towards higher ferroptosis marker malondialdehyde had no association with outcome, except for the small subset of patients with very high catalytic iron independently associated with reduced survival. Forty percent of patients did not have a clear signature of the cell death mechanisms studied in this cohort. Moreover, repeated moderate levels of soluble receptor of advanced glycation end products and growth differentiation factor 15 during the first three days after ICU admission are independently associated with adverse clinical outcome compared to sustained lower levels. Altogether, the data point towards distinct subgroups in this cohort of critical COVID-19 patients with different systemic signatures of pyroptosis, iron dyshomeostasis, ferroptosis or pneumocyte cell death markers that have different outcomes in ICU. The distinct groups may allow 'personalized' treatment allocation in critical COVID-19 based on systemic biomarker profiles.}},
  author       = {{Peleman, Cédric and Van Coillie, Samya and Ligthart, Symen and Choi, Sze Men and De Waele, Jan and Depuydt, Pieter and Benoit, Dominique and SCHAUBROECK, HANNAH and Francque, Sven M. and Dams, Karolien and Jacobs, Rita and Robert, Dominique and Roelandt, Ria and Seurinck, Ruth and Saeys, Yvan and Rajapurkar, Mohan and Jorens, Philippe G. and Hoste, Eric and Vanden Berghe, Tom}},
  issn         = {{1350-9047}},
  journal      = {{CELL DEATH AND DIFFERENTIATION}},
  keywords     = {{Cell Biology,Molecular Biology}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{2066--2077}},
  publisher    = {{Springer Science and Business Media LLC}},
  title        = {{Ferroptosis and pyroptosis signatures in critical COVID-19 patients}},
  url          = {{http://doi.org/10.1038/s41418-023-01204-2}},
  volume       = {{30}},
  year         = {{2023}},
}
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