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Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Educational Objective
To review characteristics of critically ill patients during the COVID-19 epidemic 
1 Credit CME
Key Points

Question  What clinical characteristics are associated with the development of acute respiratory distress syndrome (ARDS) and progression from ARDS to death among patients with coronavirus disease 2019 (COVID-19) pneumonia?

Findings  In this cohort study involving 201 patients with confirmed COVID-19 pneumonia, risk factors associated with the development of ARDS and progression from ARDS to death included older age, neutrophilia, and organ and coagulation dysfunction. Treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Meaning  Risk for developing ARDS included factors consistent with immune activation; older age was associated with both ARDS development and death, likely owing to less robust immune responses.

Abstract

Importance  Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.

Objective  To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died.

Design, Setting, and Participants  Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020.

Exposures  Confirmed COVID-19 pneumonia.

Main Outcomes and Measures  The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed.

Results  Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72).

Conclusions and Relevance  Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

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Article Information

Published Online: March 13, 2020. doi:10.1001/jamainternmed.2020.0994

Correction: This article was corrected on May 11, 2020, to fix data errors and correct units of measure used in the Results section and Tables 2, 3, and 4.

Accepted for Publication: March 3, 2020.

Corresponding Authors: Yuanlin Song, MD, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China (ylsong70_02@163.com); Junhua Zheng, MD, Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 85 Wujin Rd, Shanghai 200080, China (zhengjh0471@sina.com).

Author Contributions: Drs Song and Zheng had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Wu, X. Chen, Cai, and Xia contributed equally and share first authorship. Drs Song and Zheng contributed equally to the study.

Study concept and design: Wu, X. Chen, Cai, Xia, Zheng, Y. Song.

Acquisition, analysis, or interpretation of data: X. Chen, Xing Zhou, S. Xu, Huang, L. Zhang, Xia Zhou, Du, Y. Zhang, J. Song, Wang, Chao, Yang, J. Xu, Xin Zhou, D. Chen, Xiong, L. Xu, F. Zhou, Jiang, Bai.

Drafting of the manuscript: X. Chen, Xia, Xing Zhou, S. Xu, Huang, L. Zhang, Xia Zhou, Du, Y. Zhang, J. Song, Wang, Chao, Yang, J. Xu, Xin Zhou, D. Chen, Xiong, L. Xu, F. Zhou, Jiang, Bai.

Critical revision of the manuscript for important intellectual content: Wu, X. Chen, Cai, Xia, Du, Zheng, Y. Song.

Statistical analysis: X. Chen, Y. Song.

Obtained funding: Wu, Zheng, Y. Song.

Administrative, technical, or material support: Cai, Xia, Xing Zhou, S. Xu, Huang, L. Zhang, Xia Zhou, Yang, J. Xu, Xin Zhou, D. Chen, Xiong, L. Xu, F. Zhou, Jiang, Bai, Zheng, Y. Song.

Study supervision: Zheng, Y. Song.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by a grant from Prevention and Treatment of Infection in Novel Coronavirus Pneumonia Patients from the Shanghai Science and Technology Committee (to Dr Yuanlin Song), the Special Fund of Shanghai Jiaotong University for Coronavirus Disease 2019 Control and Prevention (2020RK47 to Dr Junhua Zheng), and Academic Leader of Shanghai Qingpu District Healthcare Commission (WD2019-36 to Dr Chaomin Wu).

Role of the Funder/Sponsor The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Weibing Wang, PhD, from the Department of Epidemiology, School of Public Health, Fudan University; Yan Liu, MD, and Hongcai Shang, PhD, from Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine; Xiaojia Huang, PhD, from the Institute of Biomedical Engineering and Health Sciences, Changzhou University; and Yaohui Li, MD, from Zhongshan Hospital, Fudan University for their statistical analysis discussion. We also thank Dongni Hou, MD, Sucheng Mu, MD, Donghui Zhang, MD, and Ke Lang, BD, from Zhongshan Hospital, Fudan University for their data collection. They were not compensated for their contributions.

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