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Supplementary appendix

Clinical characteristics of 2019 novel coronavirus infection in China

Wei-jie Guan 1*, Ph.D., Zheng-yi Ni 2*, M.D., Yu Hu 3*, M.D., Wen-hua Liang 1,4*, Ph. D., Chun-quan Ou 5*, MSc., Jian-xing He 1,6*, M.D., Lei Liu 7,8*, M.D., Hong Shan 9*, M.D., Chun-liang Lei 10*, M.D., David S.C. Hui 11*, M.D., Bin Du 12*, M.D., Lan-juan Li 13*, M.D., Guang Zeng 14*, MSc., Kwok-Yung Yuen 15*, Ph.D., Ru-chong Chen 1, M.D., Chun-li Tang 1, M.D., Tao Wang 1, M.D., Ping-yan Chen 4, M.D., Jie Xiang 2, M.D., Shi-yue Li 1, M.D., Jin-lin Wang 1, M.D., Zi-jing Liang 16, M.D., Yi-xiang Peng 17, M.D., Li Wei 18, M.D., Yong Liu 19, M.D., Ya-hua Hu 20, M.D., Peng Peng 21, M.D., Jian-ming Wang 22, M.D., Ji-yang Liu 23, M.D., Zhong Chen 24, M.D., Gang Li 25, M.D., Zhi-jian Zheng 26, M.D., Shao-qin Qiu 27, M.D., Jie Luo 28, M.D., Chang-jiang Ye 29, M.D., Shao-yong Zhu 30, M.D., Nan-shan Zhong 1, M.D., on behalf of China Medical Treatment Expert Group for 2019-nCoV

1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China

2. Wuhan Jin-yintan Hospital, Wuhan, Hubei, China

3. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China

4. Department of Thoracic Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

5. State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China

6. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

7. Shenzhen Third People’s Hospital, Shenzhen, China

8. The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China

9. The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China

10. Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China

11. Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China

12. Medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking, China

13. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

14. Chinese Center for Disease Control and Prevention, Beijing, China

15. Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China

16. Department of Emergency Room, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

17. The Central Hospital of Wuhan, Wuhan, Hubei, China

18. Wuhan No.1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, Hubei, China

19. Chengdu Public Health Clinical Medical Center, Chengdu, Sichuan, China

20. Huangshi Central Hospital of Edong Healthcare Group, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, China

21. Wuhan Pulmonary Hospital, Wuhan, 430030, Hubei, China

22. Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430065, China

23. The First Hospital of Changsha, Changsha 410005, Hunan, China

24. The Third People's Hospital of Hainan Province, Sanya, 572000, Hainan, China

25. Huanggang Central Hospital, Huanggang, Hubei, China

26. Wenling First People's Hospital, Wenling, Zhejiang, China

27. The Third People's Hospital of Yichang, Yichang, 443000, Hubei Province, China

28. Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, China

29. Xiantao First People's Hospital, Xiantao, China

30. The People's Hospital of Huangpi District, Wuhan, China

* Drs. Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng and Yuen contributed equally to the article.

Corresponding author: Nan-Shan Zhong. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, China. Tel.: +86-20-83062729; Fax: +86-20-83062729; E-mail: nanshan@vip.

Methods

Definitions of exposure and clinical complications

** In our study, exposure to wildlife denoted that a person in close contact with wildlife animals (bats, snakes, civet cats, etc.) or visiting either a wildlife retailer or a market selling wildlife within two weeks before the onset of respiratory symptoms. The cases with regular visit to the market without recalling the exposure date were, however, not considered as having definite exposure to the wildlife [E1].

** Pneumonia was diagnosed as an acute respiratory disorder characterized by the presence of cough and at least one of the new-onset focal chest signs, fever for more than 4 days or dyspnoea/ tachypnoea, which were in accordance with the chest radiograph findings of lung shadowing [E2].

** Shock and acute respiratory distress syndrome (ARDS) were defined in accordance with the WHO interim guidance [E3].

** Acute kidney injury was defined based on the highest serum creatinine level and urine output [E4]. Specifically, the diagnosis could be made based on any of the following criterion: an increase in serum creatinine levels by 0.3 mg/dl or greater (26.5 µmol/l or greater) within 48 hours; or increase in serum creatinine levels to 1.5 times of the baseline level or greater, which was known or presumed to have occurred within 7 days; or urine volume of below 0.5 ml/kg/h for 6 consecutive hours.

** The diagnosis of secondary bacterial or fungal infection was made in case of the occurrence of hospital-acquired pneumonia or bacteremia, plus a positive result of new pathogen culture from the blood and lower respiratory tract specimen (including sputum, bronchoalveolar lavage fluid or tracheal aspirate) obtained at least 8 hours after admission [E5].

** Acute heart failure was defined as the a clinical syndrome characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality [E6].

** Rhabdomyolysis was diagnosed if the muscle pain or muscle weakness took place on admission and the creatine kinase level was greater than 10 times the upper limit of normal [E7].

Laboratory testing

Laboratory confirmation of the 2019-nCoV was achieved through the concerted efforts of the Chinese Center for Disease Prevention and Control (CDC), the Chinese Academy of Medical Science, Academy of Military Medical Sciences, and Wuhan Institute of Virology.

The reverse-transcriptase polymerase chain reaction (RT-PCR) assay was conducted in accordance with the protocol established by the World Health Organization. Details of nucleic acids extraction have been published recently [E5]. Extraction of nucleic acids from the respiratory samples was performed with a High Pure Viral Nucleic Acid Kit. The extracted nucleic acids were tested for the 2019-nCoV.

The following sequences of 2019-nCoV were adopted for the RT-PCR assays: forward primer 5′-TCAGAATGCCAATCTCCCCAAC-3′; reverse primer 5′-AAAGGTCCACCCGATACATTGA-3′; probe 5′CY5-CTAGTTACACTAGCCATCCTTACTGC-3′BHQ1. Amplifications were initially done at 50°C for 15 min and subsequently at 95°C for 3 min, followed by 45 cycles of 95°C for 15 s and 60°C for 30 s [E5].

Reference

E1. Gao HN, Lu HZ, Cao B, et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 2013;368:2277-85

E2. Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management of adult lower respiratory tract infections – Summary. Clin Microbiol Infect 2011; 17 (Suppl. 6): 1–24

E3. WHO. Clinical management of severe acute respiratory infection when Novel coronavirus (nCoV) infection is suspected: interim guidance. Jan 11, 2020.

of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected (accessed February 4th, 2020)

E4. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. March, 2012. (accessed on January 30, 2020)

E5. Huang C, Wang Y, Li X, et al. Clinical features of patients with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; doi: 10.1016/S0140-6736(20)30183-5

E6. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-2200

E7. Graham DJ, Staffa JA, Shatin D, et al. Incidence of Hospitalized Rhabdomyolysis in

Patients Treated With Lipid-Lowering Drugs. JAMA 2004;292:2585-90

E8. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015;386:995-1007

E9. Wang C, Horby PW, Heyden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020; doi: 10.1016/S0140-6736(20)30185-9

E10. 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. doi: 10.1016/S0140-6736(20)30211-7

E11. Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020; doi: 10.1016/S0140-6736(20)30154-9

W12. Lu R, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications of virus origins and receptor binding. Lancet. 2020; doi: 10.1016/S0140-6736(20)30251-8

E133. Yang W, Lipsitch M, Shaman J. Inference of seasonal and pandemic influenza transmission dynamics. Proc Natl Acad Sci U S A. 2015;112:2723-8

E14. Paules C, Subbarao K. Influenza. Lancet. 2017;390:697-708

E15. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza. Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus Infection. N Engl J Med 2010; 362:1708-1719

E16. Wijngaard CC, Asten Lv, Koopmans MP, et al. Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children. PLoS One. 2012;7:e31197

Results

Tables

Table E1. Risk factors associated with the composite endpoint in univariate competing risk model

|Parameter (N) |Stratification |Composite endpoint |

| | |HR |CI |P.value |

|Age (1011) |>65 yrs vs. ................
................

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