Claim CME

Coronavirus (COVID19)

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

JAMA Internal Medicine

March 13, 2020

Original Investigation

Article Information and Disclosures

Chaomin Wu, MD^1,2,3; Xiaoyan Chen, MD³; Yanping Cai, MD²; et al Jia’an Xia, MD⁴; Xing Zhou, MD²; Sha Xu, MD²; Hanping Huang, MD⁴; Li Zhang, MD⁴; Xia Zhou, MD⁴; Chunling Du, MD¹; Yuye Zhang, BD³; Juan Song, BD³; Sijiao Wang, BD³; Yencheng Chao, MD³; Zeyong Yang, MD⁵; Jie Xu, MD⁶; Xin Zhou, MD⁷; Dechang Chen, MD⁸; Weining Xiong, MD⁹; Lei Xu, MD¹⁰; Feng Zhou, MD¹; Jinjun Jiang, MD³; Chunxue Bai, MD^3,11; Junhua Zheng, MD¹²; Yuanlin Song, MD^1,3,11,13 Author Affiliations

¹Department of Pulmonary Medicine, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
²Infection Division, Wuhan Jinyintan Hospital, Wuhan, China
³Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
⁴Tuberculosis and Respiratory Department, Wuhan Jinyintan Hospital, Wuhan, China
⁵Department of Anesthesiology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
⁶Department of Infectious Diseases, Fengxian Guhua Hospital, Shanghai, China
⁷Department of Pulmonary Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
⁸Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
⁹Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
¹⁰Department of Emergency Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, China
¹¹Shanghai Respiratory Research Institute, Shanghai, China
¹²Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
¹³National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China

Read article on JAMA Network

Read Article Claim 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.

Claim CME

Buy This Activity

Article Information

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).

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

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.

References

World Health Organization. Coronavirus disease 2019 (COVID-19): situation report—37. February 25, 2020. Accessed February 26, 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200226-sitrep-37-covid-19.pdf?sfvrsn=6126c0a4_2.

Zhu N, Zhang D, Wang W, et al; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733. doi:10.1056/NEJMoa2001017 PubMed Google Scholar Crossref

Huang C, Wang Y, Li X, et al Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5 Google Scholar Crossref

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513. doi:10.1016/S0140-6736(20)30211-7 PubMed Google Scholar Crossref

Wang D, Hu B, Hu C, et al Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. Published online February 7, 2020. doi:10.1001/jama.2020.1585 Google Scholar

World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. January 28, 2020. Accessed March 5, 2020. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected.

Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):243-250. doi:10.1056/NEJM199701233360402 PubMed Google Scholar Crossref

Schell-Chaple HM, Puntillo KA, Matthay MA, Liu KD; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Body temperature and mortality in patients with acute respiratory distress syndrome. Am J Crit Care. 2015;24(1):15-23. doi:10.4037/ajcc2015320 PubMed Google Scholar Crossref

Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529-539. doi:10.1007/s00281-017-0629-x PubMed Google Scholar Crossref

10.

Wang YH, Lin AS, Chao TY, et al. A cluster of patients with severe acute respiratory syndrome in a chest ward in southern Taiwan. Intensive Care Med. 2004;30(6):1228-1231. doi:10.1007/s00134-004-2311-8 PubMed Google Scholar Crossref

11.

Nicholls JM, Poon LLM, Lee KC, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003;361(9371):1773-1778. doi:10.1016/S0140-6736(03)13413-7 PubMed Google Scholar Crossref

12.

Ng DL, Al Hosani F, Keating MK, et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014. Am J Pathol. 2016;186(3):652-658. doi:10.1016/j.ajpath.2015.10.024 PubMed Google Scholar Crossref

13.

Min CK, Cheon S, Ha NY, et al. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci Rep. 2016;6:25359. doi:10.1038/srep25359 PubMed Google Scholar Crossref

14.

Kim ES, Choe PG, Park WB, et al. Clinical progression and cytokine profiles of Middle East respiratory syndrome coronavirus infection. J Korean Med Sci. 2016;31(11):1717-1725. doi:10.3346/jkms.2016.31.11.1717 PubMed Google Scholar Crossref

15.

Lew TW, Kwek TK, Tai D, et al. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290(3):374-380. doi:10.1001/jama.290.3.374 PubMed Google Scholar Crossref

16.

Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM. Naive T cell maintenance and function in human aging. J Immunol. 2015;194(9):4073-4080. doi:10.4049/jimmunol.1500046 PubMed Google Scholar Crossref

17.

Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. Published online February 3, 2020. doi:10.1038/s41586-020-2012-7 PubMed Google Scholar

18.

Hoffmann M, Kleine-Weber H, Krüger N, Müller M, Drosten C, Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor 2 ACE2 and the cellular protease TMPRSS2 for entry into target cells. Preprint. Posted online January 31, 2020. bioRxiv. doi:10.1101/2020.01.31.929042

19.

Gu J, Gong E, Zhang B, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202(3):415-424. doi:10.1084/jem.20050828 PubMed Google Scholar Crossref

20.

Li T, Qiu Z, Zhang L, et al. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J Infect Dis. 2004;189(4):648-651. doi:10.1086/381535 PubMed Google Scholar Crossref

21.

Cui W, Fan Y, Wu W, Zhang F, Wang JY, Ni AP. Expression of lymphocytes and lymphocyte subsets in patients with severe acute respiratory syndrome. Clin Infect Dis. 2003;37(6):857-859. doi:10.1086/378587 PubMed Google Scholar Crossref

22.

Kim KD, Zhao J, Auh S, et al. Adaptive immune cells temper initial innate responses. Nat Med. 2007;13(10):1248-1252. doi:10.1038/nm1633 PubMed Google Scholar Crossref

23.

Zhao J, Zhao J, Perlman S. T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice. J Virol. 2010;84(18):9318-9325. doi:10.1128/JVI.01049-10 PubMed Google Scholar Crossref

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

Editorial Concern—Possible Reporting of the Same Patients With COVID-19 in Different Reports

See More About

If you are not a JN Learning subscriber, you can either:

A subscription to JN Learning (CME from JAMA Network) provides:

Sign in to access

If you are not a JN Learning subscriber, you can either:

Sign in to customize your interests

With a personal account, you can:

Name Your Search

Sign in to save your search

With a personal account, you can:

Lookup An Activity

My Saved Searches

Sign in to customize your interests

With a personal account, you can:

Purchase access