Prognostic significance of cytokine dysregulation in critically ill COVID-19 patients

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-01-27 DOI:10.1016/j.cyto.2025.156867

Fabian Fellipe Bueno Lemos , Luana Weber Lopes , Gabriel Carvalho Brito , Airton Idalecio Sousa Viana , Caroline Tianeze de Castro , Marcel Silva Luz , André Pereira Gonçalves , Rafael Santos Dantas Miranda Dórea , Filipe Antônio França da Silva , Breno Bittencourt de Brito , Maria Luísa Cordeiro Santos , Geovani Moreno Santos Júnior , Maria Teresa Araújo de Lorenzo Barcia , Renata de Amorim Marques , André Bezerra Botelho , Anna Carolina Saúde Dantas , Fillipe Dantas Pinheiro , Adriano Fernandes Teixeira , Cláudio Lima Souza , Márcio Vasconcelos Oliveira , Fabrício Freire de Melo

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引用次数: 0

Abstract

Background

Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes—particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU).

Methods

We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation.

Results

Deceased patients exhibited significantly higher levels of interleukin (IL)-1β, IL-2, IL-6, transforming growth factor (TGF)-β, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1β and TGF-β had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity.

Conclusion

Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies.

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COVID-19危重症患者细胞因子失调的预后意义

背景：了解COVID-19的免疫发病机制为预测不良后果（特别是死亡率）提供了有价值的见解。然而，我们对所提出的病理生理机制之间复杂的相互作用的理解仍然存在重大差距。在此，我们的目的是调查重症监护病房（ICU）未接种COVID-19疫苗的危重患者死亡率相关的免疫学因素。方法：我们进行了一项单中心前瞻性研究，纳入了56例未接种疫苗的ICU患者。采用酶联免疫吸附法（ELISA）定量测定入院时血浆细胞因子水平。连续变量表示为中位数（IQR），分类变量表示为频率和百分比。非参数检验评估组间差异。Logistic回归和受试者工作特征（ROC）曲线分析确定了死亡率的预测因子，采用自举法(1000次重新抽样；95% BCa CI)进行模型验证。结果：与幸存者相比，死亡患者的白细胞介素(IL)-1β、IL-2、IL-6、转化生长因子(TGF)-β和干扰素(IFN)-γ水平显著升高。相反，IL-10和IL-27与有利的结果相关。Logistic回归模型确定IL-2和IFN-γ水平升高是死亡率的重要预测因子。值得注意的是，个体ROC曲线分析显示IL-1β和TGF-β对死亡率具有极好的判别能力，而IFN-γ、IL-2和IL-27具有极好的判别能力。结论：我们的研究结果表明，在未接种疫苗的危重COVID-19患者中，存活者与非存活者存在不同的细胞因子谱。这些发现强调了细胞因子失调在严重COVID-19病例中的重要性，并提出了预后方法的潜在靶点。需要进一步的研究来验证这些结果，并将其转化为有效的临床管理策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.