Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients.

IF 27.1 1区 医学 Q1 CRITICAL CARE MEDICINE Intensive Care Medicine Pub Date : 2024-11-01 Epub Date: 2024-08-26 DOI:10.1007/s00134-024-07593-3
Niklas Bruse, Anna Motos, Rombout van Amstel, Eckart de Bie, Emma J Kooistra, Aron Jansen, Dirk van Lier, Jason Kennedy, Daniel Schwarzkopf, Daniel Thomas-Rüddel, Jesus F Bermejo-Martin, Ferran Barbe, Nicolette F de Keizer, Michael Bauer, Johannes G van der Hoeven, Antoni Torres, Christopher Seymour, Lonneke van Vught, Peter Pickkers, Matthijs Kox
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Abstract

Purpose: Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect.

Methods: We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes.

Results: We derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2-9] after ICU admission and administered for 5 [3-7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09-2.31], p = 0.015 and HR 1.79 [1.42-2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76-1.54], p = 0.654).

Conclusion: Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment.

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临床表型发现 COVID-19 重症患者的皮质类固醇治疗与存活率之间存在异质性关联。
目的:2019年冠状病毒病(COVID-19)的疾病异质性可能会使目前 "一刀切 "的治疗方法变得不理想。我们旨在确定 COVID-19 重症患者的临床表型和免疫学特征,并评估皮质类固醇治疗效果的异质性:我们对 2020 年 2 月至 2022 年 2 月期间入住 82 家荷兰重症监护病房的 13279 名 COVID-19 患者在入住重症监护病房(ICU)后 24 小时内获得的 21 项临床参数进行了一致的 K-均值聚类。在西班牙 6225 名 COVID-19 ICU 患者(2020 年 2 月至 2021 年 12 月)中再现了衍生表型。在荷兰和德国的三个 COVID-19 ICU 队列中进行了纵向免疫学特征描述,并评估了不同表型中皮质类固醇治疗与生存之间的关系:结果:我们得出了三种表型:COVIDICU1(43% 的患者)由年轻患者组成,他们的急性生理学和慢性健康评估(APACHE)评分最低,体重指数(BMI)最高,PaO2/FiO2 比率最低,90 天院内死亡率为 18%。与 COVIDICU1 相比,COVIDICU2 患者(37%)的体重指数(BMI)最低,年龄较大,APACHE 评分较高,死亡率(24%)也较高。COVIDICU3 患者(20%)年龄最大,合并症最多,APACHE 评分最高,急性肾损伤和代谢紊乱最严重,死亡率最高(47%)。这些患者的炎症反应也最为明显。ICU 入院后第 5 天[2-9]开始皮质类固醇治疗并持续 5 天[3-7],与 COVIDICU1 和 COVIDICU2 表型患者 90 天死亡风险的增加有关(危险比 [HR] 1.59 [1.09-2.31],p = 0.015 和 HR 1.79 [1.42-2.26],p 结论:COVIDICU1 和 COVIDICU2 表型患者的 90 天死亡风险增加:我们的跨国研究发现了三种不同的 COVID-19 临床表型,每种表型在人口统计学、临床和免疫学特征以及对后期和短期皮质类固醇治疗的反应方面都存在明显差异。
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来源期刊
Intensive Care Medicine
Intensive Care Medicine 医学-危重病医学
CiteScore
51.50
自引率
2.80%
发文量
326
审稿时长
1 months
期刊介绍: Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.
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