Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19.
Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19.
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DOI：
10.1038/s41598-021-95431-7
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发表时间：
2021-08-05
影响因子：
4.6
通讯作者：
Schenck EJ
中科院分区：
文献类型：
--
作者：
Su C;Xu Z;Hoffman K;Goyal P;Safford MM;Lee J;Alvarez-Mulett S;Gomez-Escobar L;Price DR;Harrington JS;Torres LK;Martinez FJ;Campion TR Jr;Wang F;Schenck EJ
COVID-19相关的呼吸衰竭提供了前所未有的机会来评估宿主对统一病原性损伤的不同反应。了解严重COVID-19是否存在不同的亚表型可能有助于深入了解其病理生理学。序贯器官衰竭评估（SOFA）评分是一种客观和全面的测量方法，可测量六个器官系统的功能障碍严重程度，即，心血管、中枢神经系统、凝血、肝脏、肾脏和呼吸。我们的目的是识别和表征COVID-19危重疾病的不同亚表型，这些亚表型由SOFA评分的插管后轨迹定义。纽约市两家医院的插管COVID-19患者被用作开发和验证队列。根据基线插管后SOFA将患者分为轻度、中度和重度分层。在每个层内进行分层凝聚聚类，以基于通过动态时间规整评价的SOFA评分轨迹之间的相似性来检测亚表型。在每个分层中确定了不同的恶化和恢复亚表型，其具有不同的插管后7天SOFA进展趋势。在每个分层中，恶化的亚表型患者的死亡率高于恢复的亚表型患者（轻度分层，29.7% vs. 10.3%，p = 0.033;中度分层，29.3% vs. 8.0%，p = 0.002;重度分层，53.7% vs. 22.2%，p < 0.001）。各分层与进展相关的病理生理学生物标志物不同，包括提示基线疾病严重程度较低的炎症与基线疾病严重程度较高的噬血细胞性淋巴组织细胞增多症的结果。研究结果表明，插管后COVID-19呼吸衰竭存在明显的恶化和恢复亚表型，这比基线疾病严重程度更能预测结局。不同基线疾病严重程度下的不同进展生物标志物表明COVID-19呼吸衰竭进展中的异质性病理生物学。
COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Failure Assessment (SOFA) score is an objective and comprehensive measurement that measures dysfunction severity of six organ systems, i.e., cardiovascular, central nervous system, coagulation, liver, renal, and respiration. Our aim was to identify and characterize distinct subphenotypes of COVID-19 critical illness defined by the post-intubation trajectory of SOFA score. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p = 0.033; intermediate stratum, 29.3% vs. 8.0%, p = 0.002; severe stratum, 53.7% vs. 22.2%, p < 0.001). Pathophysiologic biomarkers associated with progression were distinct at each stratum, including findings suggestive of inflammation in low baseline severity of illness versus hemophagocytic lymphohistiocytosis in higher baseline severity of illness. The findings suggest that there are clear worsening and recovering subphenotypes of COVID-19 respiratory failure after intubation, which are more predictive of outcomes than baseline severity of illness. Distinct progression biomarkers at differential baseline severity of illness suggests a heterogeneous pathobiology in the progression of COVID-19 respiratory failure.
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影响因子：
76.2
作者：
Calfee, Carolyn S.;Delucchi, Kevin;Parsons, Polly E.;Thompson, B. Taylor;Ware, Lorraine B.;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
影响因子：
15.1
作者：
Dumas, Guillaume;Demoule, Alexandre;Azoulay, Elie
通讯作者：
Azoulay, Elie
影响因子：
15.1
作者：
Karakike, Eleni;Kyriazopoulou, Evdoxia;Giamarellos-Bourboulis, Evangelos J.
通讯作者：
Giamarellos-Bourboulis, Evangelos J.
影响因子：
9.6
作者：
Rice, Todd W.;Wheeler, Arthur P.;Ware, Lorraine B.
通讯作者：
Ware, Lorraine B.
DOI：
10.1164/rccm.202004-1037cp
发表时间：
2020-06-01
影响因子：
24.7
作者：
Griffin, Kelly M.;Karas, Maria G.;Lief, Lindsay
通讯作者：
Lief, Lindsay