新型冠状病毒肺炎与非新型冠状病毒肺炎急性呼吸窘迫综合征的特定病程血液生物标志物及预后（APEL-COVID研究）：一项前瞻性观察性队列研究
Process-Specific Blood Biomarkers and Outcomes in COVID-19 Versus Non-COVID-19 ARDS (APEL-COVID Study): A Prospective, Observational Cohort Study.
作者信息
Lesur Olivier, Segal Eric David, Rego Kevin, Mercat Alain, Asfar Pierre, Chagnon Frédéric
机构信息
Centre de Recherche Clinique du CHU Sherbrooke (CRCHUS), Department of Intensive Care Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Départements de Soins Intensifs et Service de Pneumologie, CHU Sherbrooke, 3001, 12th Avenue Nord, Sherbrooke QC J1H 5N4, Canada.
出版信息
J Clin Med. 2024 Oct 4;13(19):5919. doi: 10.3390/jcm13195919.
Severe acute respiratory syndrome (SARS) and acute respiratory distress syndrome (ARDS) are often considered separate clinico-radiological entities. Whether these conditions also present a single process-specific systemic biomolecular phenotype and how this relates to patient outcomes remains unknown. A prospective cohort study was conducted, including adult patients admitted to the ICU and general floors for COVID-19-related (COVID+) or non-COVID-19-related (COVID-) acute respiratory failure during the main phase of the pandemic. The primary objective was to study blood biomarkers and outcomes among different groups and severity subsets. A total of 132 patients were included, as follows: 67 COVID+, 54 COVID- (with 11 matched control subjects for biomarker reference), and 58 of these patients allowed for further pre- and post-analysis. The baseline apelin (APL) levels were higher in COVID+ patients ( < 0.0001 vs. COVID- patients) and in SARS COVID+ patients ( ≤ 0.02 vs. ARDS), while the IL-6 levels were higher in ARDS COVID- patients ( ≤ 0.0001 vs. SARS). Multivariable logistic regression analyses with cohort biomarkers and outcome parameters revealed the following: (i) log-transformed neprilysin (NEP) activity was significantly higher in COVID+ patients (1.11 [95% CI: 0.4-1.9] vs. 0.37 [95% CI: 0.1-0.8], fold change (FC): 1.43 [95% CI: 1.04-1.97], = 0.029) and in SARS patients (FC: 1.65 [95% CI: 1.05-2.6], = 0.032 vs. non-SARS COVID+ patients, and 1.73 [95% CI: 1.19-2.5], = 0.005 vs. ARDS COVID- patients) and (ii) higher lysyl oxidase (LOX) activity and APL levels were respectively associated with death and a shorter length of hospital stay in SARS COVID+ patients (Odds Ratios (OR): 1.01 [1.00-1.02], = 0.05, and OR: -0.007 [-0.013-0.0001], = 0.048). Process-specific blood biomarkers exhibited distinct profiles between COVID+ and COVID- patients, and across stages of severity. NEP and LOX activities, as well as APL levels, are particularly linked to COVID+ patients and their outcomes (ClinicalTrials.gov Identifier: NCT04632732).
严重急性呼吸综合征（SARS）和急性呼吸窘迫综合征（ARDS）通常被视为不同的临床-放射学实体。这些病症是否也呈现单一的特定病程系统性生物分子表型，以及这与患者预后如何相关，仍不清楚。我们进行了一项前瞻性队列研究，纳入了在疫情主要阶段因新型冠状病毒肺炎相关（COVID+）或非新型冠状病毒肺炎相关（COVID-）急性呼吸衰竭入住重症监护病房（ICU）和普通病房的成年患者。主要目的是研究不同组和严重程度亚组中的血液生物标志物及预后情况。共纳入132例患者，具体如下：67例COVID+患者，54例COVID-患者（其中11例为用于生物标志物参考的匹配对照受试者），这些患者中有58例可进行进一步的前后分析。COVID+患者的基线apelin（APL）水平较高（与COVID-患者相比，<0.0001），SARS COVID+患者的基线APL水平也较高（与ARDS患者相比，≤0.02），而ARDS COVID-患者的白细胞介素-6（IL-6）水平较高（与SARS患者相比，≤0.0001）。对队列生物标志物和预后参数进行多变量逻辑回归分析，结果如下：（i）COVID+患者中经对数转换的中性内肽酶（NEP）活性显著更高（1.11[95%置信区间：0.4 - 1.9] 对比0.37[95%置信区间：0.1 - 0.8]，倍数变化（FC）：1.43[95%置信区间：1.04 - 1.97]，P = 0.029），SARS患者中的NEP活性也显著更高（与非SARS COVID+患者相比，FC：1.65[95%置信区间：1.05 - 2.6]，P = 0.032；与ARDS COVID-患者相比，FC：1.73[95%置信区间：1.19 - 2.5]，P = 0.005）；（ii）在SARS COVID+患者中，赖氨酰氧化酶（LOX）活性较高和APL水平较高分别与死亡和住院时间缩短相关（优势比（OR）：1.01[1.00 - 1.02]，P = 0.05，以及OR：-0.007[-0.013 - 0.0001]，P = 0.048）。特定病程的血液生物标志物在COVID+和COVID-患者之间以及不同严重程度阶段呈现出不同的特征。NEP和LOX活性以及APL水平与COVID+患者及其预后尤其相关（ClinicalTrials.gov标识符：NCT04632732）。
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