Ranjeva Sylvia, Pinciroli Riccardo, Hodell Evan, Mueller Ariel, Hardin C Corey, Thompson B Taylor, Berra Lorenzo
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston MA 02114, USA.
Pulmonary Critical Care Division, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston MA 02114, USA.
EClinicalMedicine. 2021 Apr;34:100829. doi: 10.1016/j.eclinm.2021.100829. Epub 2021 Apr 15.
Acute respiratory distress syndrome (ARDS) secondary to coronavirus disease-2019 (COVID-19) is characterized by substantial heterogeneity in clinical, biochemical, and physiological characteristics. However, the pathophysiology of severe COVID-19 infection is poorly understood. Previous studies established clinical and biological phenotypes among classical ARDS cohorts, with important therapeutic implications. The phenotypic profile of COVID-19 associated ARDS remains unknown.
We used latent class modeling via a multivariate mixture model to identify phenotypes from clinical and biochemical data collected from 263 patients admitted to Massachusetts General Hospital intensive care unit with COVID-19-associated ARDS between March 13 and August 2, 2020.
We identified two distinct phenotypes of COVID-19-associated ARDS, with substantial differences in biochemical profiles despite minimal differences in respiratory dynamics. The minority phenotype (class 2, = 70, 26·6%) demonstrated increased markers of coagulopathy, with mild relative hyper-inflammation and dramatically increased markers of end-organ dysfunction (e.g., creatinine, troponin). The odds of 28-day mortality among the class 2 phenotype was more than double that of the class 1 phenotype (40·0% vs.· 23·3%, OR = 2·2, 95% CI [1·2, 3·9]).
We identified distinct phenotypic profiles in COVID-19 associated ARDS, with little variation according to respiratory physiology but with important variation according to systemic and extra-pulmonary markers. Phenotypic identity was highly associated with short-term mortality. The class 2 phenotype exhibited prominent signatures of coagulopathy, suggesting that vascular dysfunction may play an important role in the clinical progression of severe COVID-19-related disease.
2019冠状病毒病（COVID-19）继发的急性呼吸窘迫综合征（ARDS）在临床、生化和生理特征上具有显著的异质性。然而，严重COVID-19感染的病理生理学仍知之甚少。先前的研究在经典ARDS队列中确立了临床和生物学表型，具有重要的治疗意义。与COVID-19相关的ARDS的表型特征仍然未知。
我们通过多变量混合模型使用潜在类别建模，从2020年3月13日至8月2日入住麻省总医院重症监护病房的263例患有COVID-19相关ARDS的患者收集的临床和生化数据中识别表型。
我们识别出两种不同的与COVID-19相关的ARDS表型，尽管呼吸动力学差异最小，但生化特征存在显著差异。少数表型（2类，n = 70，26.6%）表现出凝血功能障碍标志物增加，伴有轻度相对炎症反应增强和终末器官功能障碍标志物显著增加（如肌酐、肌钙蛋白）。2类表型的28天死亡率是1类表型的两倍多（40.0%对23.3%，OR = 2.2，95%CI [1.2, 3.9]）。
我们在与COVID-19相关的ARDS中识别出不同的表型特征，根据呼吸生理学变化不大，但根据全身和肺外标志物有重要变化。表型特征与短期死亡率高度相关。2类表型表现出明显的凝血功能障碍特征，表明血管功能障碍可能在严重COVID-19相关疾病的临床进展中起重要作用。
