老年（≥65岁）COVID-19患者的生存因素与代谢发病机制：一项多中心研究

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study.

作者信息

Mei Qi, Wang Amanda Y, Bryant Amy, Yang Yang, Li Ming, Wang Fei, Du Shangming, Kurts Christian, Wu Patrick, Ma Ke, Wu Liang, Chen Huawen, Luo Jinlong, Li Yong, Hu Guangyuan, Yuan Xianglin, Li Jian

机构信息

Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

The Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.

出版信息

Front Med (Lausanne). 2021 Jan 7;7:595503. doi: 10.3389/fmed.2020.595503. eCollection 2020.

DOI:10.3389/fmed.2020.595503

PMID:33585504

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7873923/

Abstract

Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19. In this multi-center study, elderly patients (age ≥65 years old) with laboratory-confirmed COVID-19 from 4 Wuhan hospitals were included. The clinical end point was hospital discharge or deceased with last date of follow-up on Jul. 08, 2020. Clinical, demographic, and laboratory data were collected. Univariate and multivariate analysis were performed to analyze survival and risk factors. A metabolic flux analysis using a large-scale molecular model was applied to investigate the pathogenesis of SARS-CoV-2 with regard to metabolism pathways. A total of 223 elderly patients infected with COVID-19 were included, 91 (40.8%) were discharged and 132 (59.2%) deceased. Acute respiratory distress syndrome (ARDS) developed in 140 (62.8%) patients, 23 (25.3%) of these patients survived. Multivariate analysis showed that potential risk factors for mortality were elevated D-Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], = 0.005), high immune-related metabolic index (6.42 [95% CI 2.66-15.48], < 0.001), and increased neutrophil-to-lymphocyte ratio (1.08 [95% 1.03-1.13], < 0.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI 0.17-0.51], < 0.001). Based on these factors, an algorithm (AlgSurv) was developed to predict survival for elderly patients. The metabolic flux analysis showed that 12 metabolic pathways including phenylalanine (odds ratio: 28.27 [95% CI 10.56-75.72], < 0.001), fatty acid (15.61 [95% CI 6.66-36.6], < 0.001), and pyruvate (12.86 [95% CI 5.85-28.28], < 0.001) showed a consistently lower flux in the survivors vs. the deceased subgroup. This may reflect a key pathogenic mechanism of COVID-19 infection. Several factors such as interferon atmotherapy and recreased activity of specific metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, a survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Dysregulation of the metabolic pathways revealed in this study may aid in the drug and vaccine development against COVID-19.

摘要

据报道，感染新型冠状病毒肺炎（COVID-19）的老年患者面临的死亡风险大幅增加。临床特征、治疗选择和潜在生存因素仍在研究中。本研究旨在填补这一空白，并提供与COVID-19老年患者生存相关的临床相关因素。在这项多中心研究中，纳入了来自武汉4家医院的实验室确诊COVID-19的老年患者（年龄≥65岁）。临床终点为出院或死亡，最后随访日期为2020年7月8日。收集了临床、人口统计学和实验室数据。进行单因素和多因素分析以分析生存情况和危险因素。应用基于大规模分子模型的代谢通量分析来研究严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在代谢途径方面的发病机制。共纳入223例感染COVID-19的老年患者，91例（40.8%）出院，132例（59.2%）死亡。140例（62.8%）患者发生急性呼吸窘迫综合征（ARDS），其中23例（25.3%）存活。多因素分析显示，死亡的潜在危险因素为D-二聚体升高（比值比：1.13[95%置信区间1.04 - 1.22]，P = 0.005）、高免疫相关代谢指数（6.42[95%置信区间2.66 - 15.48]，P < 0.001）和中性粒细胞与淋巴细胞比值升高（1.08[95%置信区间1.03 - 1.13]，P < 0.001）。接受干扰素雾化治疗的老年患者生存概率增加（0.29[95%置信区间0.17 - 0.51]，P < 0.001）。基于这些因素，开发了一种算法（AlgSurv）来预测老年患者的生存情况。代谢通量分析显示，包括苯丙氨酸（比值比：28.27[95%置信区间10.56 - 75.72]，P < 0.001）、脂肪酸（15.61[95%置信区间