Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China

Ruchong Chen, Wenhua Liang, Mei Jiang, Weijie Guan, Chen Zhan, Tao Wang, Chunli Tang, Ling Sang, Jiaxing Liu, Zhengyi Ni, Yu Hu, Lei Liu, Hong Shan, Chunliang Lei, Yixiang Peng, Li Wei, Yong Liu, Yahua Hu, Peng Peng, Jianming Wang, Jiyang Liu, Zhong Chen, Gang Li, Zhijian Zheng, Shaoqin Qiu, Jie Luo, Changjiang Ye, Shaoyong Zhu, Xiaoqing Liu, Linling Cheng, Feng Ye, Jinping Zheng, Nuofu Zhang, Yimin Li, Jianxing He, Shiyue Li, Nanshan Zhong, Medical Treatment Expert Group for COVID-19, Ruchong Chen, Wenhua Liang, Mei Jiang, Weijie Guan, Chen Zhan, Tao Wang, Chunli Tang, Ling Sang, Jiaxing Liu, Zhengyi Ni, Yu Hu, Lei Liu, Hong Shan, Chunliang Lei, Yixiang Peng, Li Wei, Yong Liu, Yahua Hu, Peng Peng, Jianming Wang, Jiyang Liu, Zhong Chen, Gang Li, Zhijian Zheng, Shaoqin Qiu, Jie Luo, Changjiang Ye, Shaoyong Zhu, Xiaoqing Liu, Linling Cheng, Feng Ye, Jinping Zheng, Nuofu Zhang, Yimin Li, Jianxing He, Shiyue Li, Nanshan Zhong, Medical Treatment Expert Group for COVID-19

Abstract

Background: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain.

Research question: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model.

Study design and methods: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19.

Results: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation.

Interpretation: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

Keywords: COVID-19; fatal outcome; nomogram; risk factors.

Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
A-C, Clinical characteristics of 50 fatal cases with coronavirus disease 2019. The percentages of coexisting chronic illness in fatal cases (A), treatments in fatal cases (B), and complications in fatal cases (C). ARF = acute renal failure; CRRT = continuous renal replacement therapy; DIC = disseminated intravascular coagulation; ECMO = extracorporeal membrane oxygenation; IMV = invasive mechanical ventilation; NIV = noninvasive ventilation.
Figure 2
Figure 2
Risk factor of the fatal outcome in the multivariate Cox proportional hazards regression model. The figure presents the HRs and the 95% CIs associated with the end point. AST = aspartate aminotransferase; CHD = coronary heart disease; CVD = cerebrovascular disease; HR = hazard ratio; PCT = procalcitonin; TBIL = total bilirubin.
Figure 3
Figure 3
Kaplan-Meier survival plots for different prognostic factors. The figure displays the Kaplan-Meier survival plots according to (A) age, (B) CHD, (C) CVD, (D) dyspnea, (E) PCT, and (F) AST. See Figure 2 legend for expansion of abbreviations.
Figure 4
Figure 4
Prognostic nomogram for predicting the overall survival probability of patients with coronavirus disease 2019. Prognostic patient’s value is located on each variable axis, and a line is drawn upward to determine the number of point nomogram for predicting overall survival probability of patients with coronavirus disease 2019. The sum of these numbers is located on the Total Points axis, and a line is drawn downward to the survival axes to determine the likelihood of 14-day, 21-day, and 28-day survival. See Figure 2 legend for expansion of abbreviations.
Figure 5
Figure 5
Calibration curves of the nomogram predicting OS in patients with coronavirus disease 2019. Calibration curves of the nomogram predict 14-day (A), 21-day (B), and 28-day (C) OS in patients with coronavirus disease 2019. Nomogram-predicted probability of OS is plotted on the x-axis; actual OS is plotted on the y-axis. OS = overall survival.

References

    1. World Health Organization Coronavirus disease 2019 (COVID-19) situation report-72.
    1. Chen N., Zhou M., Dong X. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
    1. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069.
    1. Ruan Q., Yang K., Wang W., Jiang L., Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;368(2):m641–m643.
    1. Kattan M.W. Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst. 2003;95(9):634–635.
    1. Liang W., Guan W., Chen R. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21(3):335–337.
    1. World Health Organization Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. Jan 28, 2020.
    1. Huang C., Wang Y., Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
    1. Lew T.W.K., Kwek T.K., Tai D. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290(3):374–380.
    1. Hui D.S., Azhar E.I., Kim Y.J., Memish Z.A., Oh M.D., Zumla A. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis. 2018;18(8):e217–e227.
    1. Wrapp D., Wang N., Corbett K.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263.
    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention [published online ahead of print February 24, 2020]. JAMA.10.1001/jama.2020.2648.
    1. Wei M., Yuan J., Liu Y., Fu T., Yu X., Zhang Z.J. Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020;323(13):1313–1314.
    1. Novel Coronavirus Pneumonia Emergency Response Epidemiology Team The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145–151. [in Chinese]
    1. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published online ahead of print, February 24, 2020] [published correction appears in Lancet Respir Med. 2020;8(4):e26]. Lancet Respir Med.10.1016/S2213-2600(20)30079-5.
    1. Lu R., Zhao X., Li J. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574.
    1. Zhou P., Yang X.L., Wang X.G. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273.
    1. Patel V.B., Zhong J.C., Grant M.B., Oudit G.Y. Role of the ACE2/angiotensin 1-7 axis of the renin-angiotensin system in heart failure. Circ Res. 2016;118(8):1313–1326.
    1. Wösten-van Asperen R.M., Lutter R., Specht P.A. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. J Pathol. 2011;225(4):618–627.
    1. Kuba K., Imai Y., Rao S. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875–879.
    1. Xu Z., Shi L., Wang Y. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. [published correction appears in Lancet Respir Med. 2020;8(4):e26.
    1. Ding L., Wang L., Ma W., He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Crit Care. 2020;24(1) 28-28.
    1. Messika J., Ben Ahmed K., Gaudry S. Use of high-flow nasal cannula oxygen therapy in subjects with ARDS: a 1-year observational study. Respir Care. 2015;60(2):162–169.
    1. de Jong E., van Oers J.A., Beishuizen A. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819–827.
    1. Schuetz P., Beishuizen A., Broyles M. Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use. Clin Chem Lab Med. 2019;57(9):1308–1318.

Source: PubMed

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