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Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called “cytokine storm” is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 146...

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Autores principales: Ebihara, Takeshi, Matsumoto, Hisatake, Matsubara, Tsunehiro, Togami, Yuki, Nakao, Shunichiro, Matsuura, Hiroshi, Kojima, Takashi, Sugihara, Fuminori, Okuzaki, Daisuke, Hirata, Haruhiko, Yamamura, Hitoshi, Ogura, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790049/
https://www.ncbi.nlm.nih.gov/pubmed/35095877
http://dx.doi.org/10.3389/fimmu.2021.798338
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author Ebihara, Takeshi
Matsumoto, Hisatake
Matsubara, Tsunehiro
Togami, Yuki
Nakao, Shunichiro
Matsuura, Hiroshi
Kojima, Takashi
Sugihara, Fuminori
Okuzaki, Daisuke
Hirata, Haruhiko
Yamamura, Hitoshi
Ogura, Hiroshi
author_facet Ebihara, Takeshi
Matsumoto, Hisatake
Matsubara, Tsunehiro
Togami, Yuki
Nakao, Shunichiro
Matsuura, Hiroshi
Kojima, Takashi
Sugihara, Fuminori
Okuzaki, Daisuke
Hirata, Haruhiko
Yamamura, Hitoshi
Ogura, Hiroshi
author_sort Ebihara, Takeshi
collection PubMed
description INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called “cytokine storm” is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 1463 plasma proteins, validate these cytokines, and compare them with sepsis. MATERIALS AND METHODS: In a derivation cohort of 306 patients with COVID-19, 1463 unique plasma proteins were measured on days 1, 4, and 8. Cytokines associated with disease severity and prognosis were derived. In a validation cohort of 62 COVID-19 patients and 38 sepsis patients treated in the intensive care unit [ICU], these derived cytokines were measured on days 1 (day of ICU admission), 2-3, and 6-8 (maximum: 3 time points/patient). Derived cytokines were compared with healthy controls and between COVID-19 and sepsis patients, and the associations with prognosis were evaluated. The time to wean off mechanical ventilation (MV) was evaluated only for COVID-19. RESULTS: IL-6, amphiregulin, and growth differentiation factor (GDF)-15 were associated with disease severity and prognosis in the derivation cohort. In the validation cohort, IL-6 and GDF-15 were elevated in COVID-19 and sepsis on day 1, and the levels of these cytokines were higher in sepsis than in COVID-19. IL-6 and GDF-15 were associated with prognosis in sepsis. Cox proportional hazards model with time as a dependent covariate showed a significant relationship between plasma GDF-15 level and time to wean off MV (hazard ratio, 0.549 [95% confidence level, 0.382–0.789]). The GDF-15 level at ICU admission predicted late recovery. CONCLUSION: GDF-15 and IL-6 derived from proteomics analysis were related with disease severity of COVID-19. Their values were higher in sepsis than in COVID-19 and were associated with prognosis in sepsis. In COVID-19 patients treated in the ICU, GDF-15 was associated with the time to wean off MV and better predicted late recovery.
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spelling pubmed-87900492022-01-27 Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis Ebihara, Takeshi Matsumoto, Hisatake Matsubara, Tsunehiro Togami, Yuki Nakao, Shunichiro Matsuura, Hiroshi Kojima, Takashi Sugihara, Fuminori Okuzaki, Daisuke Hirata, Haruhiko Yamamura, Hitoshi Ogura, Hiroshi Front Immunol Immunology INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called “cytokine storm” is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 1463 plasma proteins, validate these cytokines, and compare them with sepsis. MATERIALS AND METHODS: In a derivation cohort of 306 patients with COVID-19, 1463 unique plasma proteins were measured on days 1, 4, and 8. Cytokines associated with disease severity and prognosis were derived. In a validation cohort of 62 COVID-19 patients and 38 sepsis patients treated in the intensive care unit [ICU], these derived cytokines were measured on days 1 (day of ICU admission), 2-3, and 6-8 (maximum: 3 time points/patient). Derived cytokines were compared with healthy controls and between COVID-19 and sepsis patients, and the associations with prognosis were evaluated. The time to wean off mechanical ventilation (MV) was evaluated only for COVID-19. RESULTS: IL-6, amphiregulin, and growth differentiation factor (GDF)-15 were associated with disease severity and prognosis in the derivation cohort. In the validation cohort, IL-6 and GDF-15 were elevated in COVID-19 and sepsis on day 1, and the levels of these cytokines were higher in sepsis than in COVID-19. IL-6 and GDF-15 were associated with prognosis in sepsis. Cox proportional hazards model with time as a dependent covariate showed a significant relationship between plasma GDF-15 level and time to wean off MV (hazard ratio, 0.549 [95% confidence level, 0.382–0.789]). The GDF-15 level at ICU admission predicted late recovery. CONCLUSION: GDF-15 and IL-6 derived from proteomics analysis were related with disease severity of COVID-19. Their values were higher in sepsis than in COVID-19 and were associated with prognosis in sepsis. In COVID-19 patients treated in the ICU, GDF-15 was associated with the time to wean off MV and better predicted late recovery. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC8790049/ /pubmed/35095877 http://dx.doi.org/10.3389/fimmu.2021.798338 Text en Copyright © 2022 Ebihara, Matsumoto, Matsubara, Togami, Nakao, Matsuura, Kojima, Sugihara, Okuzaki, Hirata, Yamamura and Ogura https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ebihara, Takeshi
Matsumoto, Hisatake
Matsubara, Tsunehiro
Togami, Yuki
Nakao, Shunichiro
Matsuura, Hiroshi
Kojima, Takashi
Sugihara, Fuminori
Okuzaki, Daisuke
Hirata, Haruhiko
Yamamura, Hitoshi
Ogura, Hiroshi
Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
title Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
title_full Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
title_fullStr Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
title_full_unstemmed Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
title_short Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
title_sort cytokine elevation in severe covid-19 from longitudinal proteomics analysis: comparison with sepsis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790049/
https://www.ncbi.nlm.nih.gov/pubmed/35095877
http://dx.doi.org/10.3389/fimmu.2021.798338
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